Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.
An HLA-DR antigen which is associated with HLA-DRB1 CHAINS encoded by DRB1*03 alleles.
Substances that are recognized by the immune system and induce an immune reaction.
A subclass of HLA-D antigens that consist of alpha and beta chains. The inheritance of HLA-DR antigens differs from that of the HLA-DQ ANTIGENS and HLA-DP ANTIGENS.
An HLA-DR antigen which is associated with HLA-DRB1 CHAINS encoded by DRB1*04 alleles.
HLA-DR antigen subtypes that have been classified according to their affinity to specific ANTIBODIES. The DNA sequence analyses of HLA-DR ALPHA-CHAINS and HLA-DR BETA-CHAINS has for the most part revealed the specific alleles that are responsible for each serological subtype.
Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.
A group of the D-related HLA antigens found to differ from the DR antigens in genetic locus and therefore inheritance. These antigens are polymorphic glycoproteins comprising alpha and beta chains and are found on lymphoid and other cells, often associated with certain diseases.
Substances elaborated by bacteria that have antigenic activity.
A broad specificity HLA-DR antigen that is associated with HLA-DRB1 CHAINS encoded by DRB1*01:15 and DRB1*01:16 alleles.
Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.
Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Substances elaborated by viruses that have antigenic activity.
Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen.
T-cell receptors composed of CD3-associated alpha and beta polypeptide chains and expressed primarily in CD4+ or CD8+ T-cells. Unlike immunoglobulins, the alpha-beta T-cell receptors recognize antigens only when presented in association with major histocompatibility (MHC) molecules.
IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.
The body's defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Membrane proteins in precursor B-LYMPHOCYTES (pre-B Cells). They are composed of membrane-bound MU IMMUNOGLOBULIN HEAVY CHAINS in complex with SURROGATE LIGHT CHAINS instead of conventional IMMUNOGLOBULIN LIGHT CHAINS. Only successful rearrangement of the VDJ segments, at the Ig heavy chain gene locus (IMMUNOGLOBULIN HEAVY CHAIN GENES), will generate mu heavy chains that can pair with surrogate light chains. Thus formation of the pre-B cell receptors is an important checkpoint in the development of mature B cells.
Sites on an antigen that interact with specific antibodies.
A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.
Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).
A HLA-DR antigen that is associated with HLA-DRB1 CHAINS encoded by DRB1*07 alleles.
An HLA-DR antigen associated with HLA-DRB1 CHAINS that are encoded by DRB1*01 alleles.
Identification of the major histocompatibility antigens of transplant DONORS and potential recipients, usually by serological tests. Donor and recipient pairs should be of identical ABO blood group, and in addition should be matched as closely as possible for HISTOCOMPATIBILITY ANTIGENS in order to minimize the likelihood of allograft rejection. (King, Dictionary of Genetics, 4th ed)
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Drying and inflammation of the conjunctiva as a result of insufficient lacrimal secretion. When found in association with XEROSTOMIA and polyarthritis, it is called SJOGREN'S SYNDROME.
The major group of transplantation antigens in the mouse.
Any part or derivative of any protozoan that elicits immunity; malaria (Plasmodium) and trypanosome antigens are presently the most frequently encountered.
A variable mixture of the mono- and disodium salts of gold thiomalic acid used mainly for its anti-inflammatory action in the treatment of rheumatoid arthritis. It is most effective in active progressive rheumatoid arthritis and of little or no value in the presence of extensive deformities or in the treatment of other forms of arthritis.
Genetic loci in the vertebrate major histocompatibility complex that encode polymorphic products which control the immune response to specific antigens. The genes are found in the HLA-D region in humans and in the I region in mice.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.
Differentiation antigens found on thymocytes and on cytotoxic and suppressor T-lymphocytes. CD8 antigens are members of the immunoglobulin supergene family and are associative recognition elements in MHC (Major Histocompatibility Complex) Class I-restricted interactions.
Antibodies produced by a single clone of cells.
A subtype of HLA-DRB beta chains that includes over one hundred allele variants. The HLA-DRB1 subtype is associated with several of the HLA-DR SEROLOGICAL SUBTYPES.
Membrane glycoproteins consisting of an alpha subunit and a BETA 2-MICROGLOBULIN beta subunit. In humans, highly polymorphic genes on CHROMOSOME 6 encode the alpha subunits of class I antigens and play an important role in determining the serological specificity of the surface antigen. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during GRAFT REJECTION and restrict cell-mediated lysis of virus-infected cells.
Antigenic determinants recognized and bound by the T-cell receptor. Epitopes recognized by the T-cell receptor are often located in the inner, unexposed side of the antigen, and become accessible to the T-cell receptors after proteolytic processing of the antigen.
A group of antigens that includes both the major and minor histocompatibility antigens. The former are genetically determined by the major histocompatibility complex. They determine tissue type for transplantation and cause allograft rejections. The latter are systems of allelic alloantigens that can cause weak transplant rejection.
Polyomavirus antigens which cause infection and cellular transformation. The large T antigen is necessary for the initiation of viral DNA synthesis, repression of transcription of the early region and is responsible in conjunction with the middle T antigen for the transformation of primary cells. Small T antigen is necessary for the completion of the productive infection cycle.
Polymorphic class I human histocompatibility (HLA) surface antigens present on almost all nucleated cells. At least 20 antigens have been identified which are encoded by the A locus of multiple alleles on chromosome 6. They serve as targets for T-cell cytolytic responses and are involved with acceptance or rejection of tissue/organ grafts.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
Class I human histocompatibility (HLA) surface antigens encoded by more than 30 detectable alleles on locus B of the HLA complex, the most polymorphic of all the HLA specificities. Several of these antigens (e.g., HLA-B27, -B7, -B8) are strongly associated with predisposition to rheumatoid and other autoimmune disorders. Like other class I HLA determinants, they are involved in the cellular immune reactivity of cytolytic T lymphocytes.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
T-cell receptors composed of CD3-associated gamma and delta polypeptide chains and expressed primarily in CD4-/CD8- T-cells. The receptors appear to be preferentially located in epithelial sites and probably play a role in the recognition of bacterial antigens. The T-cell receptor gamma/delta chains are separate and not related to the gamma and delta chains which are subunits of CD3 (see ANTIGENS, CD3).
Established cell cultures that have the potential to propagate indefinitely.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Substances of fungal origin that have antigenic activity.
Any part or derivative of a helminth that elicits an immune reaction. The most commonly seen helminth antigens are those of the schistosomes.
A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*02 allele family.
A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.
Antigens expressed on the cell membrane of T-lymphocytes during differentiation, activation, and normal and neoplastic transformation. Their phenotypic characterization is important in differential diagnosis and studies of thymic ontogeny and T-cell function.
The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.
An encapsulated lymphatic organ through which venous blood filters.
Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. CD4 antigens are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. CD4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120.
A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.
A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the response to colon cancer treatment.
Human immune-response or Class II antigens found mainly, but not exclusively, on B-lymphocytes and produced from genes of the HLA-D locus. They are extremely polymorphic families of glycopeptides, each consisting of two chains, alpha and beta. This group of antigens includes the -DR, -DQ and -DP designations, of which HLA-DR is most studied; some of these glycoproteins are associated with certain diseases, possibly of immune etiology.
Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.
Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.
A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence.
A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.
The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.
Receptors that are specifically found on the surface of NATURAL KILLER CELLS. They play an important role in regulating the cellular component of INNATE IMMUNITY.
Those proteins recognized by antibodies from serum of animals bearing tumors induced by viruses; these proteins are presumably coded for by the nucleic acids of the same viruses that caused the neoplastic transformation.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.
A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.
Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).
Theoretical representations that simulate the behavior or activity of immune system, processes, or phenomena. They include the use of mathematical equations, computers, and other electrical equipment.
Ordered rearrangement of T-cell variable gene regions coding for the antigen receptors.
Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.
The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX.
A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.
Molecule composed of the non-covalent association of the T-cell antigen receptor (RECEPTORS, ANTIGEN, T-CELL) with the CD3 complex (ANTIGENS, CD3). This association is required for the surface expression and function of both components. The molecule consists of up to seven chains: either the alpha/beta or gamma/delta chains of the T-cell receptor, and four or five chains in the CD3 complex.
High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain a cytoplasmic protein tyrosine phosphatase activity which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. The CD45 antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons.
DNA sequences encoding the beta chain of the T-cell receptor. The genomic organization of the TcR beta genes is essentially the same in all species and is similar to the organization of Ig genes.
Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
Glycoproteins found on the membrane or surface of cells.
The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.
A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.
Molecules on the surface of B- and T-lymphocytes that recognize and combine with specific antigens.
Glycoproteins expressed on cortical thymocytes and on some dendritic cells and B-cells. Their structure is similar to that of MHC Class I and their function has been postulated as similar also. CD1 antigens are highly specific markers for human LANGERHANS CELLS.
Three regions (CDR1; CDR2 and CDR3) of amino acid sequence in the IMMUNOGLOBULIN VARIABLE REGION that are highly divergent. Together the CDRs from the light and heavy immunoglobulin chains form a surface that is complementary to the antigen. These regions are also present in other members of the immunoglobulin superfamily, for example, T-cell receptors (RECEPTORS, ANTIGEN, T-CELL).
A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure MONOCLONAL ANTIBODIES or T-cell products, identical to those produced by the immunologically competent parent cell.
Class I human histocompatibility (HLA) antigens encoded by a small cluster of structural genes at the C locus on chromosome 6. They have significantly lower immunogenicity than the HLA-A and -B determinants and are therefore of minor importance in donor/recipient crossmatching. Their primary role is their high-risk association with certain disease manifestations (e.g., spondylarthritis, psoriasis, multiple myeloma).
Ordered rearrangement of T-cell variable gene regions coding for the beta-chain of antigen receptors.
Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.
Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.
Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
The lipopolysaccharide-protein somatic antigens, usually from gram-negative bacteria, important in the serological classification of enteric bacilli. The O-specific chains determine the specificity of the O antigens of a given serotype. O antigens are the immunodominant part of the lipopolysaccharide molecule in the intact bacterial cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
Immunoglobulins produced in a response to BACTERIAL ANTIGENS.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
A serine protease that catalyses the release of an N-terminal dipeptide. Several biologically-active peptides have been identified as dipeptidyl peptidase 4 substrates including INCRETINS; NEUROPEPTIDES; and CHEMOKINES. The protein is also found bound to ADENOSINE DEAMINASE on the T-CELL surface and is believed to play a role in T-cell activation.
The processes triggered by interactions of ANTIBODIES with their ANTIGENS.
A protein tyrosine kinase that is required for T-CELL development and T-CELL ANTIGEN RECEPTOR function.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A class of animal lectins that bind to carbohydrate in a calcium-dependent manner. They share a common carbohydrate-binding domain that is structurally distinct from other classes of lectins.
Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.
Nonsusceptibility to the invasive or pathogenic effects of foreign microorganisms or to the toxic effect of antigenic substances.
DNA sequences encoding the alpha chain of the T-cell receptor. The genomic organization of the TcR alpha genes is essentially the same in all species and is similar to the organization of Ig genes.
A component of the B-cell antigen receptor that is involved in B-cell antigen receptor heavy chain transport to the PLASMA MEMBRANE. It is expressed almost exclusively in B-LYMPHOCYTES and serves as a useful marker for B-cell NEOPLASMS.
A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.
A trisaccharide antigen expressed on glycolipids and many cell-surface glycoproteins. In the blood the antigen is found on the surface of NEUTROPHILS; EOSINOPHILS; and MONOCYTES. In addition, CD15 antigen is a stage-specific embryonic antigen.
Carbohydrate antigens expressed by malignant tissue. They are useful as tumor markers and are measured in the serum by means of a radioimmunoassay employing monoclonal antibodies.
An albumin obtained from the white of eggs. It is a member of the serpin superfamily.
Proteins prepared by recombinant DNA technology.
A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*08 allele family.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
The altered state of immunologic responsiveness resulting from initial contact with antigen, which enables the individual to produce antibodies more rapidly and in greater quantity in response to secondary antigenic stimulus.
Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.
Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.
Those hepatitis B antigens found on the surface of the Dane particle and on the 20 nm spherical and tubular particles. Several subspecificities of the surface antigen are known. These were formerly called the Australia antigen.
Methods used by pathogenic organisms to evade a host's immune system.
Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.
Costimulatory T-LYMPHOCYTE receptors that have specificity for CD80 ANTIGEN and CD86 ANTIGEN. Activation of this receptor results in increased T-cell proliferation, cytokine production and promotion of T-cell survival.
Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry.
Sets of cell surface antigens located on BLOOD CELLS. They are usually membrane GLYCOPROTEINS or GLYCOLIPIDS that are antigenically distinguished by their carbohydrate moieties.
A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CTLA-4 ANTIGEN with high specificity and to CD28 ANTIGEN with low specificity. The interaction of CD80 with CD28 ANTIGEN provides a costimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
The process by which antigen is presented to lymphocytes in a form they can recognize. This is performed by antigen presenting cells (APCs). Some antigens require processing before they can be recognized. Antigen processing consists of ingestion and partial digestion of the antigen by the APC, followed by presentation of fragments on the cell surface. (From Rosen et al., Dictionary of Immunology, 1989)
Differentiation antigens expressed on B-lymphocytes and B-cell precursors. They are involved in regulation of B-cell proliferation.
Immunoglobulins produced in response to VIRAL ANTIGENS.
Ordered rearrangement of T-cell variable gene regions coding for the gamma-chain of antigen receptors.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
DNA sequences, in cells of the T-lymphocyte lineage, that code for T-cell receptors. The TcR genes are formed by somatic rearrangement (see GENE REARRANGEMENT, T-LYMPHOCYTE and its children) of germline gene segments, and resemble Ig genes in their mechanisms of diversity generation and expression.
Ordered rearrangement of T-cell variable gene regions coding for the alpha-chain of antigen receptors.
Elements of limited time intervals, contributing to particular results or situations.
Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.
They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
A member of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. It is found on mature B-LYMPHOCYTES and some EPITHELIAL CELLS, lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations of the gene for CD40 antigen result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
Genetic loci in the vertebrate major histocompatibility complex which encode polymorphic characteristics not related to immune responsiveness or complement activity, e.g., B loci (chicken), DLA (dog), GPLA (guinea pig), H-2 (mouse), RT-1 (rat), HLA-A, -B, and -C class I genes of man.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
Transmembrane proteins that form the beta subunits of the HLA-DQ antigens.
Protection from an infectious disease agent that is mediated by B- and T- LYMPHOCYTES following exposure to specific antigen, and characterized by IMMUNOLOGIC MEMORY. It can result from either previous infection with that agent or vaccination (IMMUNITY, ACTIVE), or transfer of antibody or lymphocytes from an immune donor (IMMUNIZATION, PASSIVE).
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*01 allele family.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions.
Antigens that exist in alternative (allelic) forms in a single species. When an isoantigen is encountered by species members who lack it, an immune response is induced. Typical isoantigens are the BLOOD GROUP ANTIGENS.
The interfaces between T-CELLS and ANTIGEN-PRESENTING CELLS. Supramolecular organization of proteins takes place at these synapses involving various types of immune cells. Immunological synapses can have several functions including LYMPHOCYTE ACTIVATION; enhancing, balancing, or terminating signaling; or directing cytokine secretion.
Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules.
A major histocompatibily complex class I-like protein that plays a unique role in the presentation of lipid ANTIGENS to NATURAL KILLER T-CELLS.
An inhibitory T CELL receptor that is closely related to CD28 ANTIGEN. It has specificity for CD80 ANTIGEN and CD86 ANTIGEN and acts as a negative regulator of peripheral T cell function. CTLA-4 antigen is believed to play role in inducing PERIPHERAL TOLERANCE.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Glycoprotein members of the immunoglobulin superfamily which participate in T-cell adhesion and activation. They are expressed on most peripheral T-lymphocytes, natural killer cells, and thymocytes, and function as co-receptors or accessory molecules in the T-cell receptor complex.
This enzyme is a lymphoid-specific src family tyrosine kinase that is critical for T-cell development and activation. Lck is associated with the cytoplasmic domains of CD4, CD8 and the beta-chain of the IL-2 receptor, and is thought to be involved in the earliest steps of TCR-mediated T-cell activation.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*27 allele family.
CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.
An increased reactivity to specific antigens mediated not by antibodies but by cells.
Antigens of the virion of the HEPATITIS B VIRUS or the Dane particle, its surface (HEPATITIS B SURFACE ANTIGENS), core (HEPATITIS B CORE ANTIGENS), and other associated antigens, including the HEPATITIS B E ANTIGENS.
The demonstration of the cytotoxic effect on a target cell of a lymphocyte, a mediator released by a sensitized lymphocyte, an antibody, or complement.
Ordered rearrangement of T-cell variable gene regions coding for the delta-chain of antigen receptors.
Subunits of the antigenic determinant that are most easily recognized by the immune system and thus most influence the specificity of the induced antibody.
Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.
Subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2, gamma-interferon, and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, Th1 cells are associated with vigorous delayed-type hypersensitivity reactions.
Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides SERUM SICKNESS and the ARTHUS REACTION, evidence supports a pathogenic role for immune complexes in many other IMMUNE SYSTEM DISEASES including GLOMERULONEPHRITIS, systemic lupus erythematosus (LUPUS ERYTHEMATOSUS, SYSTEMIC) and POLYARTERITIS NODOSA.
A melanosome-specific protein that plays a role in the expression, stability, trafficking, and processing of GP100 MELANOMA ANTIGEN, which is critical to the formation of Stage II MELANOSOMES. The protein is used as an antigen marker for MELANOMA cells.
A sex-specific cell surface antigen produced by the sex-determining gene of the Y chromosome in mammals. It causes syngeneic grafts from males to females to be rejected and interacts with somatic elements of the embryologic undifferentiated gonad to produce testicular organogenesis.
A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CD28 ANTIGEN with high specificity and to CTLA-4 ANTIGEN with low specificity. The interaction of CD86 with CD28 ANTIGEN provides a stimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.
Subpopulation of CD4+ lymphocytes that cooperate with other lymphocytes (either T or B) to initiate a variety of immune functions. For example, helper-inducer T-cells cooperate with B-cells to produce antibodies to thymus-dependent antigens and with other subpopulations of T-cells to initiate a variety of cell-mediated immune functions.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
Disorders caused by abnormal or absent immunologic mechanisms, whether humoral, cell-mediated, or both.
Subset of helper-inducer T-lymphocytes which synthesize and secrete the interleukins IL-4, IL-5, IL-6, and IL-10. These cytokines influence B-cell development and antibody production as well as augmenting humoral responses.
Antibody-mediated immune response. Humoral immunity is brought about by ANTIBODY FORMATION, resulting from TH2 CELLS activating B-LYMPHOCYTES, followed by COMPLEMENT ACTIVATION.
A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*07 allele family.
A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.
A classification of B-lymphocytes based on structurally or functionally different populations of cells.
Glycoproteins expressed on all mature T-cells, thymocytes, and a subset of mature B-cells. Antibodies specific for CD5 can enhance T-cell receptor-mediated T-cell activation. The B-cell-specific molecule CD72 is a natural ligand for CD5. (From Abbas et al., Cellular and Molecular Immunology, 2d ed, p156)
The immune system uses the HLAs to differentiate self cells and non-self cells. Any cell displaying that person's HLA type ... These cells have receptors that are similar to B cell receptors, and each cell recognizes only a few class II-peptide ... bound within the binding cleft portion of the HLA-DR1 molecule. In the illustration far below, a different view, one can see an ... T cells help B cells make antibodies to the same foreign antigens. Each HLA can bind many peptides, and each person has 3 HLA ...
... constitutes a ligand for the T-cell receptor (TCR). HLA (human leukocyte antigens) were originally defined as cell surface ... HLA-DR1 to HLA-DR17). The HLA-DRB3 locus encodes the HLA-DR52 specificity, is moderately variable and is variably associated ... DR is also a marker for immune stimulation. HLA-DR is an αβ heterodimer, cell surface receptor, each subunit of which contains ... These cells then bind to antigens on the surface of B-cells stimulating B-cell proliferation. The primary function of HLA-DR is ...
The immune system uses the HLAs to differentiate self cells and non-self cells. Any cell displaying that person's HLA type ... T cells have receptors that are similar to B cell receptors, and each T cell recognizes only a few MHC class II-peptide ... bound within the binding cleft portion of the HLA-DR1 molecule. In the illustration far below, a different view, one can see an ... It has been shown that high resolution HLA typing (HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 and HLA-DPB1) may be relevant in ...
antigen processing and presentation of peptide or polysaccharide antigen via MHC class II. • immune response. • T cell receptor ... 1kg0: Structure of the Epstein-Barr Virus gp42 Protein Bound to the MHC class II Receptor HLA-DR1 ... HLA class II histocompatibility antigen, DRB5 beta chain is a protein that in humans is encoded by the HLA-DRB5 gene.[5] ... 1fyt: CRYSTAL STRUCTURE OF A COMPLEX OF A HUMAN ALPHA/BETA-T CELL RECEPTOR, INFLUENZA HA ANTIGEN PEPTIDE, AND MHC CLASS II ...
"Correlation between acetylcholine receptor antibody titer and HLA-B8 and HLA-DRw3 antigens in myasthenia gravis". Trans Am ... In 1975, association with "HL-A1,8" (Current name: HLA A1-B8) was confirmed by serological typing of cells from myasthenics. ... Of the haplotypes mentions above, A24-Cw*0702::DQ2 or A1::B8-DR1-DQ5, none appear to be ancestral to A1::DQ2. An A1::DQ2 ... Also a dozen inflammatory diseases of the immune system can attribute some risk to the haplotype. Some disease like coeliac ...
"HLA-DR molecules from an antigen-processing mutant cell line are associated with invariant chain peptides". Nature. 360 (6403 ... The cell surface form of the invariant chain is known as CD74. CD74 is a cell surface receptor for the cytokine macrophage ... "Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1". Nature. 364 (6432): 33-9. Bibcode: ... Vogt AB, Kropshofer H (April 1999). "HLA-DM - an endosomal and lysosomal chaperone for the immune system". Trends in ...
Antigen presentation: MHC molecules bind to both T cell receptor and CD4/CD8 co-receptors on T lymphocytes, and the antigen ... About half have known immune functions. The human MHC is also called the HLA (human leukocyte antigen) complex (often just the ... September 2011). "Affinity maturation of human CD4 by yeast surface display and crystal structure of a CD4-HLA-DR1 complex". ... The most studied HLA genes are the nine classical MHC genes: HLA-A, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA- ...
INFLUENZA HA ANTIGEN PEPTIDE, AND MHC CLASS II MOLECULE, HLA-DR1 ... CRYSTAL STRUCTURE OF A COMPLEX OF A HUMAN ALPHA/BETA-T CELL ... HLA-DR1. *DOI: 10.2210/pdb1FYT/pdb. *Classification: IMMUNE SYSTEM. *Organism(s): Homo sapiens, Influenza A virus (strain A/ ... An alphabeta T-cell receptor (alphabetaTCR)/hemagglutinin (HA) peptide/human leukocyte antigen (HLA)-DR1 complex was stabilized ... An alphabeta T-cell receptor (alphabetaTCR)/hemagglutinin (HA) peptide/human leukocyte antigen (HLA)-DR1 complex was stabilized ...
... model of the alphabeta T cell receptor bound to the influenza haemagglutinin antigen and MHC class II molecule HLA-DR1. T cell ... or T cells), part of the bodys immune system. Antigens (foreign proteins) are presented to T cell receptors by MHC molecules ... receptors are protein complexes found on the surface of a type of white blood cell called T lymphocytes ( ... to effect an immune response. - Stock Image C025/1593 ... T cell receptor antigen complex. C025/1593 Rights Managed. ...
Minor structural changes in a mutated human melanoma antigen correspond to dramatically enhanced stimulation of a CD4+ tumor- ... Here, we present the crystal structures of HLA-DR1 in complex with both wild-type and mutant TPI peptide antigens, the first ... A flexible docking approach for prediction of T cell receptor-peptide-MHC complexes. Pierce BG, Weng Z. Protein Sci. 22 35-46 ( ... Defining the structural basis by which CD4+ T cell help is invoked in an anti-tumor immune response will likely aid the design ...
Cutting Edge: Detection of Antigen-Specific CD4+ T Cells by HLA-DR1 Oligomers Is Dependent on the T Cell Activation State ... Cutting Edge: Differential Sequestration of Plasma Membrane-Associated B Cell Antigen Receptor in Mature and Immature B Cells ... Targeting Murine Immune Responses to Selected T Cell- or Antibody-Defined Determinants of the Hepatitis B Surface Antigen by ... Both γδ T Cells and NK Cells Inhibit the Engraftment of Xenogeneic Rat Bone Marrow Cells and the Induction of Xenograft ...
The androgen receptor (AR) plays an essential role in the development and progression of prostate cancer. However, while it has ... which express human HLA-A2 and HLA-DR1, with pTVG-AR augmented AR LBD HLA-A2-restricted peptide-specific, cytotoxic immune ... Treatment with autologous antigen-presenting cells activated with the HER-2 based antigen Lapuleucel-T: results of a phase I ... A mouse model of human adaptive immune functions: HLA-A2.1-/HLA-DR1-transgenic H-2 class I-/class II-knockout mice. Eur J ...
These peptide antigens are then recognized by T-cell receptors (TCRs) specific to that peptide. Crystal structures of SAgs in ... SEB and TSST-1 in complex with HLA-DR1) and the high-affinity site SpeC in complex with HLA-DR2 and SEH in complex with HLA-DR1 ... class II molecules and T-cell receptors, which in turn is responsible for their ability to illicit an immune response several ... Conventional antigens are processed internally by antigen-presenting cells (APCs) and displayed as discrete peptides on the ...
A2/DR1 mice) have been developed to study the immunogenicity of tumor antigen-derived T cell epitopes. To extend the use and ... A mouse model of human adaptive immune functions: HLA-A2.1-/HLA-DR1-transgenic H-2 class I-/class II-knockout mice. Eur J ... The analysis of SARC-L1 tumor microenvironment revealed a strong infiltration by T cells expressing inhibitory receptors such ... HLA-A*01:03, HLA-A*24:02, HLA-B*08:01, HLA-B*27:05, HLA-B*35:01, HLA-B*44:02, and HLA-C*07:01 monochain transgenic/H-2 class I ...
Bet v 1-specific T-cell receptor/forkhead box protein 3 transgenic T cells suppress Bet v 1-specificT-cell effector function in ... Association of HLA-DR1 with the allergic response to the major mugwort pollen allergen: molecular background. BMC Immunology 13 ... T-cell-derived cytokines enhance the antigen-presenting capacity of human neutrophils. Eur J Immunol. 49(9):1441-1443. (2019) ... Neutrophils are the first immune cells to arrive at the site of injection of vaccines. We recently discovered that aluminum ...
... a T-cell line from the thymus of a myasthenia gravis patient against recombinant α subunit of the human acetylcholine receptor ... This dimorphism at position 86 is widespread, occurring in subtypes of DR1, DR2, DR3, DR5, and DR6 alleles as well as DR4. ... Helper T lymphocytes recognize fragments of foreign (or self) antigens in the peptide-binding clefts of major ... histocompatibility complex class II molecules; their activation is a crucial step in the induction of many immune and ...
... could alter the efficiency of carbohydrate receptor recognition by innate immune cells that can promote uptake of antigens, ... Summed CD4 T cell responses by HLA restriction and HA subtype. Total (A) HLA-DR1- and (B) HLA-DR4-restricted CD4 T cell ... CD4 T cell epitope locations within the viral HA protein. Peptide sequences encoding HLA-DR1- or HLA-DR4-restricted CD4 T cell ... 2 and 4.) This correlates with their lower cell surface density of HLA-DR4 relative to HLA-DR1 on dendritic cells in these two ...
The immune system uses the HLAs to differentiate self cells and non-self cells. Any cell displaying that persons HLA type ... These cells have receptors that are similar to B cell receptors, and each cell recognizes only a few class II-peptide ... bound within the binding cleft portion of the HLA-DR1 molecule. In the illustration far below, a different view, one can see an ... T cells help B cells make antibodies to the same foreign antigens. Each HLA can bind many peptides, and each person has 3 HLA ...
A mouse model of human adaptive immune functions: HLA-A2.1-/HLA-DR1-transgenic H-2 class I-/class II-knockout mice. Eur. J. ... In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination. J. Exp. Med. ... T cell and B cell responses against a range of different antigens. However, antigen coupling to antibodies is a major ... Neither CD4+ nor CD8+ T cells were susceptible to MHV-GM/GP transduction (not shown), whereas antigen-presenting cells, such as ...
In B-cells; the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) ... In addition to APCs; other cells of the gastrointestinal tract; such as epithelial cells; express MHC class II molecules and ... also to express HLA-DO. Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II ... The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM ...
Structure of a covalently stabilized complex of a human alphabeta T-cell receptor, influenza HA peptide and MHC class II ... CLASS II HISTOCOMPATIBILITY ANTIGEN (HLA-DR1) (ALPHA CHAIN) 9606 119 4P4K 1 A, E HLA class II histocompatibility antigen, DP ... MHC class II Receptor HLA-DR1 ALPHA CHAIN, EXTRACELLULAR DOMAIN 9606 117 3QIU 1 A H-2 CLASS II HISTOCOMPATIBILITY ANTIGEN, E-K ... HLA CLASS II HISTOCOMPATIBILITY ANTIGEN 9606 9 6ATF 1 A, D HLA class II histocompatibility antigen, DR alpha chain UNP residues ...
Innate immune cells are recognized for their rapid and critical contribution to the bodys first line of defense against ... Exosomes bearing HLA-DR1 molecules need dendritic cells to efficiently stimulate specific T cells. Int Immunol 14:713-722PubMed ... Mature dendritic cells secrete exosomes with strong ability to induce antigen-specific effector immune responses. Blood Cells ... Regulation of dendritic cell migration and adaptive immune response by leukotriene B4 receptors: a role for LTB4 in up- ...
... constitutes a ligand for the T-cell receptor (TCR). HLA (human leukocyte antigens) were originally defined as cell surface ... HLA-DR1 to HLA-DR17). The HLA-DRB3 locus encodes the HLA-DR52 specificity, is moderately variable and is variably associated ... DR is also a marker for immune stimulation. HLA-DR is an αβ heterodimer, cell surface receptor, each subunit of which contains ... These cells then bind to antigens on the surface of B-cells stimulating B-cell proliferation. The primary function of HLA-DR is ...
Cross-reactive antigen recognition by an encephalitogenic T cell receptor: implications for T cell biology and autoimmunity. J ... Assembly of HLA DR1 molecules translated in vitro: binding of peptide in the endoplasmic reticulum precludes association with ... A kinetic basis for T cell receptor repertoire selection during an immune response. Immunity 10:485. ... HLA-DM interactions with intermediates in HLA-DR maturation and a role for HLA-DM in stabilizing empty HLA-DR molecules. J. Exp ...
It is a human NK cell associated antigen. CD16 is a low affinity receptor for IgG which functions in phagocytosis and ADCC ... Latest observations claim that RA is set up in genetically predisposed people who have HLA-DR1 alleles which contain the ... Purpose We aimed to elucidate predictive factors for the development of immune-related adverse events (iraes) in patients ... TLRs include cell surface (eg TLR2 and TLR4) and endosomal (eg TLR3, 7, and 9) receptors, originally recognized in mammals for ...
A direct effect of HLA allele products on progression to AIDS is plausible, given their role in antigen presentation to T cells ... Products of these genes present antigenic peptide to T cells, initiating an immune response and clearance of the foreign ... A1-Cw7-B8-DR3-DQ2 andCw4-B35-DR1-DQ1) (12, 16,18), plus the quasi-species pattern of HIV-1 change in infected patients (19) are ... of genetic variants among HIV-1 strains and of host genetic differences such as variants in chemokine and chemokine receptor ...
... and IFN-γ by immune cells. Among these key cytokines lie therapeutic targets for currently approved antipsoriatic therapies. ... Various triggers, including recently identified autoantigens, Toll-like receptor agonists, chemerin, and thymic stromal ... T cells, and dendritic cells is thought to create inflammatory and pro-proliferative circuits mediated by chemokines and ... This review aims to provide a comprehensive overview on the immune-mediated mechanisms characterizing the current pathogenic ...
... volume emphasizes how newly discovered structural variations among superantigens affect their interactions with human immune ... cells. Most importantly, these structural and functional differences help explain the exacerbation of certain diseases and why ... SEB and TSST-1 in complex with HLA-DR1) and the high-affinity site SpeC in complex with HLA-DR2 and SEH in complex with HLA-DR1 ... Adaptive immunity relies on the antigen-specific B cell (BCR) and T cell (TCR) receptors to survey for pathogenic events. Upon ...
Naïve CD4+ T cells were instructed by MPLA-tDCs to be hyporesponsive to antigen-specific re-stimulation, and to suppress the ... Naïve CD4+ T cells were instructed by MPLA-tDCs to be hyporesponsive to antigen-specific re-stimulation, and to suppress the ... In conclusion MPLA-tDCs are able to modulate antigen-specific responses of both naïve and memory CD4+ T cells and might be a ... In conclusion MPLA-tDCs are able to modulate antigen-specific responses of both naïve and memory CD4+ T cells and might be a ...
Cutting edge: Detection of antigen‐specific CD4+ T cells by HLADR1 oligomers is dependent on the T cell activation state. J. ... Artificial antigen‐presenting cells as a tool to exploit the immune "synapse." Nat. Med. 6:1406‐1410. ... A binding site for the T‐cell co‐receptor CD8 on the a3 domain of HLA‐A2. Nature 345:41‐46. ... specific T cells. Both CD8+ and CD4+ antigen‐specific T cells are rare events and require that sufficient numbers of cells be ...
Inhibition of macropinocytosis blocks antigen presentation of type II collagen in vitro and in vivo in HLA-DR1 transgenic mice ... Brodlie M, Eger K, Hilkens CMU, Ward C. Airway epithelial cells as guardians of immune homeostasis?. Thorax 2009, 64(11), 1009 ... A region encompassing the FERM domain of Jak1 is necessary for binding to the cytokine receptor gp130. FEBS Letters 2001, 505(1 ... a failure of antigen-presenting cells to properly polarize helper T cells?. American Journal of Respiratory and Critical Care ...
... cell surface receptors that function to present antigen peptide fragments to T cells responsible for cell-mediated immune ... Crystal structure of CD4 mutant bound to HLA-DR1. 3t0e. Crystal structure of a complete ternary complex of T cell receptor, ... HISTOCOMPATIBILITY ANTIGEN. 1j8h. Crystal Structure of a Complex of a Human alpha/beta-T cell Receptor, Influenza HA Antigen ... MHC class II receptors display antigens for recognition by helper T cells (stimulate development of B cell clones) and ...
... immune pathology, immunodeficiency, autoimmune diseases, immune disorders, and immunotherapy. ... by the T cell receptor (TCR) on T cells [10-19]. T cells constantly scan the APC surface searching for antigens to activate and ... bound to the MHC-II molecule HLA-DR1 and an epitope from mutant triosephosphate isomerase (RCSB Protein Data Bank accession ... nearly all immune cells are influenced by TGF-β in vivo, such as T cells, B cells, natural killer cells, DCs, and macrophages. ...
... the presence of HLA-B35, HLA-DR1, HLA-DR3, HLA-DQ1 antigens was significantly associated with a bad prognosis and a rapid ... HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature 1996;381:667. ... The evolution of the immune and virologic status of both cohorts has been described elswhere (ALT: Hadida et al; Candotti et al ... MHC-HLA in humans). Combination of HLA class I (HLA-A1, HLA-A2, HLA-B14, HLA-B17, HLA-B27) and class II antigens (HLA-DR5 and ...
HLA antigens and acetylcholine receptor antibodies in penicillamine induced myasthenia gravis. Br Med J 1983;286:338-40. PMID ... Immune checkpoints, such as CTLA-4 and PD-1, are regulators that normally inhibit T-cell activation to maintain self-tolerance ... HLA antigens Bw35 and DR1 are associated with D-penicillamine-induced myasthenic syndrome; the relative absence of DR4 suggests ... PD-1 is primarily expressed on mature T cells and on other non-T cell subsets, including B cells, NK cells, and antigen- ...
EVs derived from antigen (Ag)-presenting cells for instance, have been involved in both innate and acquired (or adaptive) ... EVs derived from antigen (Ag)-presenting cells for instance, have been involved in both innate and acquired (or adaptive) ... On the other hand, tumor and stem cell derived EVs have been identified to exert an inhibitory effect on immune responses by ... On the other hand, tumor and stem cell derived EVs have been identified to exert an inhibitory effect on immune responses by ...
  • Antigens (foreign proteins) are presented to T cell receptors by MHC molecules to effect an immune response. (
  • An effective and effecient peptide binding prediction approach for a broad set of HLA-DR molecules based on ordered weighted averaging of binding pocket profiles. (
  • Bacterial SAgs possess the unique ability to cross-link major histocompatibility complex (MHC) class II molecules and T-cell receptors, which in turn is responsible for their ability to illicit an immune response several orders of magnitude greater than that of conventional peptide antigens. (
  • Conventional antigens are processed internally by antigen-presenting cells (APCs) and displayed as discrete peptides on the cell surface by MHC class II molecules. (
  • Crystal structures of SAgs in complex with MHC class II molecules via both the generic site (SEB and TSST-1 in complex with HLA-DR1) and the high-affinity site SpeC in complex with HLA-DR2 and SEH in complex with HLA-DR1 have allowed a detailed examination of these interactions. (
  • A zinc ion plays a critical role in the binding of SME-Z 2 , SpeG, and SpeH to MHC class II molecules, as the binding of all three of these toxins to LG-2 cells is significantly reduced by chelating the zinc. (
  • The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (
  • While SARC-L1 tumor cells lack HLA-DRB1*0101 expression, a very low expression of HLA-A*0201 molecules was found on these cells. (
  • We also obtained two genetically modified cell lines highly expressing either HLA-A*0201 or both HLA-A*0201/ HLA-DRB1*0101 molecules referred as SARC-A2 and SARC-A2DR1 respectively. (
  • Diversity of HLAs in the human population is one aspect of disease defense, and, as a result, the chance of two unrelated individuals with identical HLA molecules on all loci is extremely low. (
  • T cells require presentation via MHC molecules to recognize foreign antigens - a requirement known as MHC restriction . (
  • These CD4+ T cells recognize this epitope only in the context of HLA-DR4 class II molecules, of which the variants with Gly86 are absolutely required. (
  • HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. (
  • the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. (
  • Alternatively, MHC class II presentation of peptide or partially denatured Ags can occur via an Ii independent route, which involves either direct loading on the cell surface or recycling of MHC class II molecules from the cell surface into endocytic vesicles ( 13 , 14 , 15 , 16 ). (
  • HLA-DR molecules are upregulated in response to signalling. (
  • Accumulating data suggests that some of these molecules may contribute to the persistence and destruction observed in RA by providing as endogenous Toll Like Receptor (TLR) ligands (9). (
  • Native MHC molecules are expressed as cell‐surface glycoproteins capable of binding a variety of peptides generated from the degradation of self and non‐self proteins for display to T cells. (
  • class II molecules present exogenously derived antigenic peptides (~15 amino acids) to helper T cells. (
  • Besides antigen presentation, growing evidence is showing thatligation of MHC class II molecules also activates intracellular signalingpathways, frequently leading to apoptosis. (
  • Constitutive expression of MHCclass II molecules is confined to professional antigen-presenting cells(APC) of the immune system, and in nonprofessional APCs MHC class IImolecules can be induced by a variety of immune regulators. (
  • Interestingly,activated T cells from many species, with the exception of mice,synthesize and express MHC class II molecules at their cell surface. (
  • Such a structure involves massive redistribution of membrane proteins, including TCR/pMHC complexes, modulatory receptor pairs, and adhesion molecules. (
  • Identification of T cell antigens on the surface of APCs will lead to the rearrangement of intracellular and extracellular molecules at the T cell APC interface, ultimately leading to the assembly of a specialized supramolecular structure known as the immunological synapse (IS) [ 20 , 21 ]. (
  • EVs derived from antigen (Ag)-presenting cells for instance, have been involved in both innate and acquired (or adaptive) immune responses, as Ag carriers or presenters, or as vehicles for delivering active signaling molecules. (
  • Cell lines expressing CD21 but lacking expression of HLA class II molecules are resistant to infection by a recombinant EBV expressing enhanced green fluorescent protein. (
  • Two CD21-positive, HLA class II-negative cell lines, HPB-ALL and 721.174, were used to determine if the introduction of HLA-DP and/or HLA-DQ molecules to the surfaces of HLA class II-deficient cells could substitute for HLA-DR and mediate EBV entry. (
  • Susceptibility of CD21-expressing cell lines to EBfaV-GFP infection corresponds with surface expression of HLA class II molecules. (
  • Antigenic peptides (termed T cell epitopes) are assembled with major histocompatibility complex (MHC) molecules and presented on the surface of antigen-presenting cells (APCs) for T cell recognition. (
  • All these functions are based on the provision of a phenotype for the genetic identity of the individual by the MHC: either cell surface molecules or chemosensory signals. (
  • Class II molecules are expressed in antigen-presenting cells (APC: B lymphocytes, dendritic cells, macrophages). (
  • Each supertype-specific peptide in HLAsupE is annotated in terms of its cross-reactivity to HLA molecules within the same supertype. (
  • Promiscuous peptides that can be presented by multiple HLA molecules across multiple HLA supertypes were also included in this database. (
  • In the vertebrate immune system, short peptides derived from endogenous or exogenous antigens are presented by major histocompatibility complex (MHC) molecules on the surface of antigen presenting cells for recognition by T-cell receptors (TCRs). (
  • Peptides that bind to an HLA molecule with high affinity can also bind to multiple molecules within the same supertype [ 16 ]. (
  • Accordingly, activated Mϕ-2 but not Mϕ-1 down-modulated their antigen-presenting and costimulatory molecules (HLA-DR, CD86, and CD40). (
  • Since T cell recognition is MHC-restricted, and given the wide polymorphism of the different MHC molecules, distinct epitopes may be recognized by different individuals in the population. (
  • The central event in the cellular immune response to invading microorganisms is the specific recognition of foreign peptides bound to major histocompatibility complex (MHC) molecules by the a ß T cell receptor (TCR). (
  • The invasive phenotype of the immortalized cells was also reflected by the consistent expression of several metastasis-associated adhesion molecules, including α5 (eight of nine), α6 (five of nine), αV (nine of nine), β1 (nine of nine), and β3 (nine of nine) integrin subunits and the M r 67,000 laminin receptor (seven of nine). (
  • Contrary to our expectations, metastasis-promoting CD44 variant isoforms were only detected on two lines, whereas all cell lines expressed MUC18/melanoma cell adhesion molecule and intercellular adhesion molecule-1, two members of the immunoglobulin superfamily of adhesion molecules that are not frequently found on primary carcinoma cells. (
  • The invasive phenotype of the immortalized cells was mirrored by their epithelial-mesenchymal transition and the expression of several metastasis-associated molecules, which might be potential candidates for novel therapeutic targets. (
  • It would, therefore, be of great interest to identify the set of molecules that determine the affinity of epithelial tumor cells to BM. (
  • MHC molecules are are a part of the adaptive immune system of all vertebrates. (
  • While MHC molecules are continuously synthesised and make it to the cell outer part, another quite interesting thing happens inside cells: all the cell proteins undergo a turn-over, that is, they are produced, live in the cell for some time, and then undergo degradation. (
  • Now the interesting part: the peptides deriving from protein degradation, or at least some of them, will enter the Endoplasmic Reticulum, associate with the MHC molecules by interacting with a special binding groove on the MHC proteins (more on this to come), and finally end up exposed to the outside of the cells, bound to the MHC molecules. (
  • In the direct pathway, recipient T cells react to intact allogeneic MHC molecules expressed on the surface of donor cells. (
  • In contrast, donor MHC molecules (and all other proteins) shed from the graft can be taken up by host APCs and presented to recipient T cells in the context of self-MHC molecules - the indirect pathway. (
  • A direct cytotoxic T-cell attack on graft cells can be made only by T cells that recognize the graft MHC molecules directly. (
  • Structural hierarchy in the clustering of HLA class I molecules in the plasma membrane of human lymphoblastoid cells. (
  • Immunogenicity is the ability of molecules to induce an immune response. (
  • creating de-immune molecules that is to say, not inducing an immune response. (
  • CD4 T cells have a rearranged receptor that recognizes antigens as peptides presented by HLA class II molecules. (
  • These peptides (T epitopes) are derived from the degradation of the antigens into dendritic cells and have a sequence allowing them to bind to HLA class II molecules. (
  • Peptides processed from HLA-DR molecules and encompassing the shared epitope may also be presented by HLA-DQ and select CD4 αβ T cells in the thymus. (
  • It is known that αβ T cells use a highly polymorphic αβ surface receptor associated with a signal transducing unit to recognize antigenic peptides in association with class II major histocompatibility complex (MHC) molecules. (
  • Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules. (
  • Superantigens simultaneously bind to major histocompatibility complex class II molecules and T-cell receptor molecules bearing a particular V-β region. (
  • M. tuberculosis interferes with IFN-γ receptor (IFN-γR) signaling in macrophages, but the molecules responsible for this inhibition are poorly defined. (
  • HLA genes are highly polymorphic , which means that they have many different alleles , allowing them to fine-tune the adaptive immune system . (
  • This dimorphism at position 86 is widespread, occurring in subtypes of DR1, DR2, DR3, DR5, and DR6 alleles as well as DR4. (
  • Much of the variation at HLA DRB1 occurs at peptide contact positions in the binding groove, as a result many of the alleles alter the way the DR binds peptide ligands and changes the repertoire each receptor can bind. (
  • Latest observations claim that RA is set up in genetically predisposed people who have HLA-DR1 alleles which contain the distributed epitope pursuing environmental exposure, such as for example tobacco smoke or periodontal disease (4C6). (
  • The HLA class I alleles B*35 and Cw*04 were consistently associated with rapid development of AIDS-defining conditions in Caucasians. (
  • The extended survival of 28 to 40 percent of HIV-1-infected Caucasian patients who avoided AIDS for ten or more years can be attributed to their being fully heterozygous at HLA class I loci, to their lacking the AIDS-associated alleles B*35 and Cw*04 , or to both. (
  • In this work, we tried to understand whether combined genotypes of CCR5-▵32, CCR2-64I, SDF1-3′A and HLA alleles can predict the LT-NP status. (
  • Susceptibility and protection against human autoimmune diseases, including type I diabetes, multiple sclerosis, and Goodpasture disease, is associated with particular human leukocyte antigen (HLA) alleles. (
  • Associations of HLA-A, HLA-B and HLA-C alleles frequency with prevalence of herpes simplex virus infections and diseases across global populations: implication for the development of an universal CD8+ T-cell epitope-based vaccine. (
  • We examined the association of the HLA-A, HLA-B, and HLA-DRB1 alleles with the emergence of mutations in the complete protease gene and the first 330 codons of the reverse transcriptase (RT) gene of HIV-1, studying their distribution and persistence and their impact on antiviral drug therapy. (
  • We were able to confirm immune-driven selection pressure by major histocompatibility complex (MHC) class I and II alleles through the identification of HLA-associated mutations. (
  • The genetic associations of the HLA shared epitope alleles with antibodies to citrullinated peptides in rheumatoid arthritis patients indicate that T cells are providing help to B cells to produce autoantibodies, and there is increasing evidence that these autoantibodies are pathogenic in rheumatoid arthritis. (
  • The main advantage of this database is the ability to search for promiscuous T-cell epitopes based on the cross-reactivity to specific alleles or supertypes. (
  • Shared epitope positive HLA-DR alleles may shape the T-cell repertoire by presenting self peptides to CD4 T cells in the thymus. (
  • Thus, shared epitope-positive alleles impose a frame on the T-cell repertoire. (
  • Most patients with RA express particular HLA-DR alleles. (
  • In this review, we will focus on the influence of shared epitope positive HLA-DR alleles on CD4 αβ T cell repertoire selection. (
  • 2 1 The number of known HLA alleles is still growing and this trend will become even more pronounced with the wider use of high throughput sequencing methods 3 in clinical laboratories that perform histocompatibility testing. (
  • Nevertheless, despite these achievements, many patients will still not have a fully matched donor because of the extremely great diversity of HLA alleles and haplotypes. (
  • 7 4 1 As of January 2016 more than 14,000 HLA alleles have been assigned, accounting for more than 10,000 different HLA proteins ( ) ( Figure 1 ). (
  • We describe here a strategy to identify helper T-cell epitopes for HER2/neu that focuses on peptides predicted to bind to numerous histocompatibility alleles (promiscuous epitopes), which would encourage their use in therapeutic vaccines for the general cancer patient population. (
  • Individual studies have reported different results regarding the association of HLA alleles with RA in Chinese populations. (
  • It was proven to be associated with (histocompatibility locus antigen) HLA region strongly, especially with HLA-DRB1 alleles [ 3 ]. (
  • HLA-DRB1 alleles encode (70Q(R)K(R)RAA74) encoding the shared epitope (SE) (RAA amino acid pattern in positions 72 to 74 of the third hypervariable region of the DRβ1 chain) are associated with RA susceptibility [ 4 ]. (
  • SE contains HLA-DRB1 alleles representing significant genetic risk factor for RA. (
  • Some have reported that the frequency of the HLA-DRB1*0401 and *0405 alleles are significantly increased in RA patients, whereas others have found no associations [ 6 , 7 ]. (
  • This study was performed to systematically summarize the association between Chinese with RA and HLA-DRB1 alleles. (
  • The frequency of HLA-DRB1 alleles varies according to ethnic and racial background, with some alleles being extremely rare. (
  • HLA-DR53 specificity -encoded by HLA-DRB4 - is exclusively found in association with haplotypes encoding the DR4, DR7 and DR9 broad specificities (i.e., all DRB1*04, *07, *09 alleles). (
  • The latest list of officially recognized HLA-DRB alleles can be found at the ANRC site . (
  • HLA class II histocompatibility antigen, DRB5 beta chain is a protein that in humans is encoded by the HLA-DRB5 gene . (
  • Efficient vaccination against infectious agents and tumors depends on specific antigen targeting to dendritic cells (DCs). (
  • This study describes a novel vaccine approach that facilitates delivery of viral or tumor antigens to dendritic cells in vivo . (
  • Primary dendritic cells (DCs) also to express HLA-DO. (
  • Antigen-presenting cells (macrophages, B-cells and dendritic cells) are the cells in which DR are typically found. (
  • Tolerogenic dendritic cells (DCs) are a promising tool to control T cell-mediated autoimmunity. (
  • In this context, a novel and promising immunotherapeutic strategy to specifically control T cell-mediated pathologies is the use of ex vivo -modulated dendritic cells (DCs) ( 3 ). (
  • Dendritic cells have been described as the most potent antigen-presenting cells and are fundamental for the initiation of an effective immune response ( 4 ). (
  • In the current model, a crosstalk between keratinocytes, neutrophils, mast cells, T cells, and dendritic cells is thought to create inflammatory and pro-proliferative circuits mediated by chemokines and cytokines. (
  • I did my PhD research at the University of Amsterdam, where I worked on regulation of T cell immunity by dendritic cells. (
  • I then was awarded an EMBO fellowship to work on understanding how cytokines regulate T cell- and dendritic cell- function at Cancer Research UK laboratories in London. (
  • In October 2003 I joined Newcastle University, where I run a research group studying mechanisms underlying immune tolerance, and the development of dendritic cells as an immunotherapeutic tool. (
  • I am an Immunologist with research expertise in dendritic cell biology and immune regulation. (
  • i) To develop and implement a new cellular therapy with tolerogenic dendritic cells for rheumatoid arthritis and other diseases caused by a breakdown in immune tolerance. (
  • ii) To understand the mechanisms underlying immune regulation by dendritic cells in order to fuel and improve new areas of translational research. (
  • Targeting of tolerogenic dendritic cells towards heat-shock proteins: A novel therapeutic strategy for autoimmune diseases? (
  • Crossland KL, Abinun M, Arkwright PD, Cheetham TD, Pearce SH, Hilkens CMU, Lilic D. AIRE is not essential for the induction of human tolerogenic dendritic cells . (
  • Class II MHC glycoproteins are expressed on the surface of antigen-presenting cells (APC), including macrophages, dendritic cells and B cells. (
  • In addition, stem cell-derived EVs have also been reported to impair dendritic cell maturation and to regulate the activation, differentiation, and proliferation of B cells. (
  • This beneficial effect is associated with dramatically decreased maturation of draining lymph node dendritic cells. (
  • Plasmacytoid dendritic cells (PDC) are involved in innate immunity by interferon (IFN)-α production and in adaptive immunity by stimulating T cells and inducing generation of regulatory T cells (Treg). (
  • Activated dendritic cells produced both IL-12 and IL-23, but unlike Mϕ-1 they slightly reduced their IL-23 secretion after addition of IFN-γ. (
  • Dendritic cells (DCs) are highly potent phagocytes that prime naive T cells and control the development of Th1 cells ( 7 , 8 ). (
  • The goal of immunotherapy in myeloid leukemia is to boost the patient immune system or confer immunity with T cells, dendritic cells (DC), NK cells or monoclonal antibodies. (
  • Pulendran, B. Modulating vaccine responses with dendritic cells and Toll-like receptors. (
  • We offer oncolytic virus, CAR-T, and dendritic cell related documents, as well as newsletter. (
  • Scientists demonstrated that intestinal CD103 + CD11b + dendritic cell (DC) survival was dependent on interferon regulatory factor 4 (IRF4). (
  • The ability of tumor TEM to suppress tumor-specific T cell response mediated by tumor dendritic cells was measured in vitro . (
  • These NETs are web-like structures composed of cellular or mitochondrial DNA associated with toxic neutrophilic granular proteins and are supposed to serve as endogenous danger signals for the immune system. (
  • The human leukocyte antigen ( HLA ) system or complex is a gene complex encoding the major histocompatibility complex (MHC) proteins in humans. (
  • These cell-surface proteins are responsible for the regulation of the immune system in humans. (
  • The proteins encoded by certain genes are also known as antigens , as a result of their historic discovery as factors in organ transplants. (
  • MHC class I proteins associate with β2-microglobulin , which unlike the HLA proteins is encoded by a gene on chromosome 15 . (
  • Aside from the genes encoding the 6 major antigen-presenting proteins, there are a large number of other genes, many involved in immune function, located on the HLA complex. (
  • The proteins encoded by HLAs are those on the outer part of body cells that are (in effect) unique to that person. (
  • Proteins from the pathogen are digested into small pieces ( peptides ) and loaded onto HLA antigens (to be specific, MHC class II ). (
  • Through a similar process, proteins (both native and foreign, such as the proteins of virus) produced inside most cells are displayed on HLAs (to be specific, MHC class I ) on the cell surface. (
  • It is important to understand, first, if there is a general deficiency in the ability of avian hemagglutinin (HA) proteins to generate immune responses and, if so, what underlies this defect. (
  • Because of the generally high levels of cross-reactive CD4 T cells in humans, it is not possible to compare the inherent immunogenicities of avian and seasonal HA proteins in an unbiased manner. (
  • Here, we empirically examine the epitope diversity and abundance of CD4 T cells elicited by seasonal and avian HA proteins. (
  • HLA-DR1 and HLA-DR4 transgenic mice were vaccinated with purified HA proteins, and CD4 T cells to specific epitopes were identified and quantified. (
  • Therefore, we conclude that failure in responses to avian vaccines in humans is likely due to a lack of cross-reactive CD4 T cell memory perhaps coupled with competition with or suppression of naive, HA-specific CD4 T cells by memory CD4 T cells specific for more highly conserved proteins. (
  • EVs are submicron particles composed of a lipid bilayer, proteins, and nucleic acids released by cells in a regulated fashion. (
  • Tcell receptors (αβ) expressed by CD4 + cells recognize complexes of antigenic peptides bound to MHC class II proteins on the surface of APCs. (
  • proteins citrullination and these altered proteins are selectively offered by shared epitope positive antigen presenting cells, resulting in anti-citrullinated peptide antibodies (ACPA), which are characteristic of RA (3, 5). (
  • MHC II proteins present peptide antigens that originate extracellularly from foreign bodies such as bacteria. (
  • Proteins from the pathogen are degraded into peptide fragments within the APC, which sequesters these fragments into the endosome so they can bind to MHC class II proteins, before being transported to the cell surface. (
  • However, both present peptide fragments rather than entire proteins to T cells, and are required to mount an immune response. (
  • Proteasomes, cal systems, including post-infectious pro- which generate peptides from cytoplasmic tective immune responses, only some pep- proteins for the class I pathway, seem to tides from a large number of potential candi- have preferred cleavage sites flanking domi- dates are actually the target of a vigorous nant CD8+ T cell epitopes in protein se- immune response. (
  • It binds to human leukocyte antigen class II (HLA class II) proteins expressed on B cells to trigger virus-cell membrane fusion ( 6 , 7 , 10 , 16 , 25 ). (
  • The human leukocyte antigen (HLA) system or complex is a group of related proteins that are encoded by the major histocompatibility complex (MHC) gene complex in humans. (
  • Major histocompatibility complex (MHC) genes code for key proteins of the adaptive immune system, which present antigens from intra-cellular (MHC class I) and extra-cellular (MHC class II) pathogens. (
  • Weight for weight, the cell-surface bound hemolysin, streptolysin S, is one of the most toxic proteins known ( 10 ). (
  • Aim This research exams the hypothesis that DNA intercalation and electrophilic connections could be exploited to noncovalently assemble doxorubicin within a viral proteins nanoparticle made to focus on EIF4G1 and penetrate tumor cells through ligand-directed delivery. (
  • It plays a central role in the immune system by presenting peptides derived from extracellular proteins. (
  • T-cell responses to collagen type II, heat shock proteins and microbial antigens have been reported in a small proportion of RA patients (reviewed in [ 7 ]), and more recently autoantibodies to deiminated 'citrullinated' peptides have been described, suggesting that they may be important autoantigens in this disease. (
  • Only antibodies against antigens found in late endosomes precipitated infectious virus, whereas antibodies against proteins located primarily on the cell surface did not. (
  • Within an infected cell, virions are formed in a temporally and spatially coordinated manner wherein the components that make up the virus (e.g., the virally encoded envelope, Gag, protease, integrase, reverse transcriptase, and Vpr proteins, together with the RNA genome) assemble in association with a specific cellular membrane from which the viral envelope is derived. (
  • The major histocompatibility complex, which encodes proteins that present antigens on the cell surface and regulates communication between immune cells, has been shown to be associated with RA for the last 30 years [ 4 ], [ 11 ]. (
  • however, with the exception of the BCR-ABL and PML-RARα fusion proteins, such leukemia-specific antigens are rare in other myeloid leukemias. (
  • The steps involved in antigen presentation and recognition by T cells that may influence the selection of antigenic protective epitopes from whole proteins will be reviewed. (
  • Cleavage site-specific proteases and transporter proteins involved in the processing of protein antigens into peptides also seem to play a role in the selection of antigenic peptides. (
  • Proteasomes, which generate peptides from cytoplasmic proteins for the class I pathway, seem to have preferred cleavage sites flanking dominant CD8+ T cell epitopes in protein sequences (4). (
  • While the turn-over rate can change from one protein (type) to another, such is the fate of all proteins inside cells. (
  • Effector phenotype or control specific CD4 T cells of therapeutic proteins is also wanted. (
  • Unfortunately, most studies on the human repertoire have lacked this kind of accuracy, analyzing either T cell responses to proteins or peptides, or the expression of α or β T cell receptor (TCR) genes/chains by CD4 T cells. (
  • Immuno-oncology approaches that utilise T cell receptors (TCRs) are becoming highly attractive because of their potential to target virtually all cellular proteins, including cancer specific epitopes, via the recognition of peptide-human leukocyte antigen complexes (pHLA) presented at the cell surface. (
  • The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. (
  • Prime candidates are the streptococcal superantigens (SAgs), a family of highly mitogenic proteins secreted individually or in certain combinations by many Streptococcus pyogenes strains ( 7 - 10 ), although other virulence factors, such as Streptolysin O and various cell wall antigens can also cause toxic shock ( 11 ). (
  • We then established peptide-specific T-cell clones for five of these six peptides and demonstrated that the T-cell clone specific for the PSMA 459 epitope (NYTLRVDCTPLMYSL) can recognize processed antigens from recombinant PSMA proteins. (
  • Moreover, while peptide-MHC binding is a prerequisite for a T cell epitope, it alone is not sufficient. (
  • Therefore, T cell epitope identification requires further functional verification of the MHC-binding peptide using professional APCs, which are difficult to isolate, expand, and maintain. (
  • To address these issues, we have developed a facile, accurate, and high-throughput method for T cell epitope mapping by screening antigen-derived peptide libraries in complex with MHC protein displayed on yeast cell surface. (
  • Dr. BenMohamed has been involved in clinical immunology, humoral and cellular immune responses, epitope mapping, epitope improvement, and the development and optimization of sub-unit vaccines against several infectious diseases including malaria Plasmodium falciparum, human immunodeficiency virus (HIV), human cytomegalovirus (HCMV) and herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2). (
  • Induction of CTL response by a minimal epitope vaccine in HLA A*0201/DR1 transgenic mice: dependence on HLA class II restricted T(H) response. (
  • HLA-DR15 and HLA-DR1 exhibit distinct peptide repertoires and binding preferences and present the α3 epitope in different binding registers. (
  • Accordingly, we provide a mechanistic basis for the dominantly protective effect of HLA in autoimmune disease, whereby HLA polymorphism shapes the relative abundance of self-epitope specific T cells that leads to protection or causation of autoimmunity. (
  • Complex antigen presentation pathway for an HLA-A*0201-restricted epitope from Chikungunya 6K protein. (
  • HIV type 1 (HIV-1) escape mutations interfere with the processing of viral antigens by proteasomes ( 2 , 33 , 34 ) or evolve at critical binding sites within the human leukocyte antigen (HLA)-restricted CTL epitope, thereby abrogating binding to the HLA molecule or inhibiting efficient recognition by the T-cell receptor ( 13 , 28 ). (
  • The source data for the T-cell activities and HLA-binding capacities of peptides with a specific HLA restriction were extracted from public epitope databases. (
  • MHC-presented peptides that can trigger cell-mediated immune responses are termed T-cell epitopes and play a vital role in the development of epitope-based vaccines and immunotherapies against viral infections, tumors and autoimmune diseases [ 1 - 4 ]. (
  • We solve the crystal structure of ligelizumab bound to IgE, and report epitope differences between ligelizumab and omalizumab that contribute to their qualitatively distinct IgE-receptor inhibition profiles. (
  • Two opposite hypotheses propose either that the shared epitope allows the presentation of target antigenic peptides to T lymphocytes or that the shared epitope helps select the T cell repertoire. (
  • We first screened a panel of six epitope peptide candidates selected with the TEPITOPE program and found that all six peptides induced peptide-specific T-cell proliferation from one or more donors with estimated T-cell precursor frequencies of 0-4.17 × 10 −6 . (
  • Here, we present the crystal structures of HLA-DR1 in complex with both wild-type and mutant TPI peptide antigens, the first structures of tumor peptide antigen/MHC class II complexes recognized by CD4+ T cells to be reported. (
  • These peptide antigens are then recognized by T-cell receptors (TCRs) specific to that peptide. (
  • The primary function of HLA-DR is to present peptide antigens, potentially foreign in origin, to the immune system for the purpose of eliciting or suppressing T-(helper)-cell responses that eventually lead to the production of antibodies against the same peptide antigen. (
  • Since most immune responses against protein and peptide antigens are T-cell dependent, the molecular target of such vaccines is to generate at least 50-100 complexes between MHC molecule and the antigenic peptide per antigen-presenting cell, sensitizing a T cell population of appropriate clonal size and effector characteristics. (
  • T cell receptors are protein complexes found on the surface of a type of white blood cell called T lymphocytes (or T cells), part of the body's immune system. (
  • Several MHC class II-restricted tumor antigens that specifically activate such CD4+ helper T lymphocytes have now been identified, including one from a melanoma tumor that is caused by a single base-pair mutation in the glycolytic enzyme triosephosphate isomerase. (
  • HLAs corresponding to MHC class II ( DP , DM , DOA , DOB , DQ , and DR ) present antigens from outside of the cell to T-lymphocytes. (
  • The main function of major histocompatibility complex (MHC) class IImolecules is to present processed antigens, which are derived primarilyfrom exogenous sources, to CD4(+) T-lymphocytes. (
  • In a virus-free cell-cell fusion assay, enhanced secretion of gp42 promotes fusion with B lymphocytes. (
  • Foreign antigens presented by MHC class I attract T-lymphocytes called killer T-cells (also referred to as CD8-positive or cytotoxic T-cells) that destroy cells. (
  • It is believed that the consequence of cAMP decreased level can be an increased release of inflammatory mediators from leukocytes, including histamine, which causes decrease in the functional activity of T-lymphocytes via H2-receptor. (
  • Most T cells in the epithelium and adjacent to the damaged basal keratinocytes are activated CD8+ lymphocytes. (
  • Activated CD8+ T cells (and possibly keratinocytes) may release cytokines that attract additional lymphocytes into the developing lesion. (
  • Antiviral cytotoxic T lymphocytes (CTLs) kill HIV-infected cells upon the recognition of specific viral epitopes. (
  • Macfarlane Burnet capped this by realizing that it is not antibodies that are selected, but the cells that make them, and that these cells are the lymphocytes, previously thought of as passive spectators of infection (Figure 3). (
  • On encountering a complementary antigen, lymphocytes change from having scant cytoplasm to being a blast cell, with copious cytoplasm, able to replicate to form new cells. (
  • Burnet realized that the unit of immune specificity is the immunological clone, a subset of lymphocytes with identical receptors for antigen, hence his Clonal Selection Theory of acquired immunity [8]. (
  • This postulates that somatic mutations in the V (Variable region) genes of multiplying lymphocytes produce the aptly named forbidden clones of lymphocytes that cause the autoimmune diseases by reacting with a host antigen instead of a microbial one. (
  • Mϕ play a crucial role in human host defense by secreting cytokines and chemokines, presenting antigen to T lymphocytes and clearing infectious agents. (
  • First, to some extent, encoded antigens can enter the processing and presentation pathways of the immune system and induce adaptive (antibodies, helper T cells, and cytotoxic lymphocytes (CTLs) ) and innate immune responses in a manner similar to natural infection. (
  • AV and BV gene usage on peripheral blood αβ T lymphocytes was first analyzed by labeling T cells with monoclonal antibodies specific for particular Vα or Vβ families. (
  • Allorecognition of HLA allelic differences by T lymphocytes confers a higher risk of acute graft- versus -host disease (GVHD) and mortality. (
  • Most of the T-cell responses appeared to reflect a low affinity for antigen, which could be the result of immune tolerance because HER2/neu is expressed in low levels in normal cells and possibly including lymphocytes and monocytes. (
  • The Rag1 null and Rag2 null mutations prevent development of mature lymphocytes, and the B2m null and Prf1 null mutations prevent development and functional activity of mouse NK cells, respectively. (
  • Histological and genes signature analysis supported the sarcoma origin of this cell line. (
  • HLA genes have historically been identified as a result of the ability to successfully transplant organs between HLA-similar individuals. (
  • HLA-DR is encoded by several loci and several 'genes' of different function at each locus. (
  • A selective advantage against infectious disease associated with increased heterozygosity at the human major histocompatibility complex [human leukocyte antigen ( HLA ) class I and class II] is believed to play a major role in maintaining the extraordinary allelic diversity of these genes. (
  • HLA class I and class II loci located within the human major histocompatibility complex (MHC) comprise the most polymorphic set of genes known in humans ( 1-3 ). (
  • Products of these genes present antigenic peptide to T cells, initiating an immune response and clearance of the foreign material. (
  • Evolutionary and population studies have led to the general idea that the great diversity and even distribution of allelic frequencies observed in the class I and class II genes of the MHC ( HLA in humans) are maintained through selective forces, such as infectious disease morbidity ( 4 , 5 ). (
  • The chemokine receptor and chemokine genes along with the HLA genotype can serve as predictors of HIV-1 outcome for classification of HIV-1-infected subjects as LT-NPs or progressors. (
  • 3 The first candidates were the major histocompatibility complex genes (MHC-HLA in humans). (
  • More recently, several groups showed that the polymorphic genes of the chemokine receptor family and particularly the CCR5 and CCR2 genes, which were identified as coreceptors for HIV-1 entry into the cell, 12-16 also influence disease-free survival of HIV-1-infected patients. (
  • Mutations in HLA genes may be linked to autoimmune disease such as type I diabetes, and celiac disease. (
  • Nine of eleven patients genotyped for HLA-DR and DQ expressed the RA shared motif in their HLA class II genes. (
  • The 1998 Nomenclature Committee recognized more HLA genes all of which are in the class I and Ib regions: HLA-E, -F, -G, -H, -J, -K and -L 59 . (
  • The class III region has the highest gene density but some of the genes are not involved in the immune system 2;61 . (
  • Examples of genes include, but are not limited to, genes involved in immune/inflammatory regulation, antioxidant defenses, and fibrotic processes. (
  • However, human MHC (human leukocyte antigens, HLAs) genes exhibit a high level of polymorphism, and their distribution in the human population varies with ethnicity and region. (
  • In normals and patients with RA, HLA-DR genes exert a major influence on the CD4 αβ T-cell repertoire, as shown by studies of AV and BV gene usage and by BV BJ gene usage by peripheral blood CD4 αβ T-cells. (
  • Whereas identical BV, D or BJ genes can be used by many different T cell receptor β chains, the sequence of the VDJ junction that constitutes the third complementarity determining region is unique to a clone. (
  • This approach showed that HLA haplotypes exert a major influence on expression of AV and BV genes by peripheral blood T cells. (
  • Among the many factors that influence the outcome of hematopoietic stem cell transplantation (HSCT) polymorphism of the classical human leukocyte antigen (HLA) genes represents the most important barrier. (
  • Recent advances have been made in the of host factors, polymorphisms, and candidate genes associated characterization of the immune response to low-molecular- with occupational asthma may improve our understanding of weight agents. (
  • These particular antigens stimulate the multiplication of T-helper cells , which in turn stimulate antibody -producing B-cells to produce antibodies to that specific antigen. (
  • Atypical myasthenia gravis has been associated with a new class of immune checkpoint anticancer drugs, including anti-programmed cell death protein 1 and anti-cytotoxic lymphocyte-associated protein 4 monoclonal antibodies. (
  • A pathogenic theory of schizophrenia posits its proximate cause to be an infection during early development whereby antigens, similar to that found in CNS tissue, give rise to auto-antibodies that act against the brain. (
  • 4. Bossus M, BenMohamed L, Londono A, Barbier B, Tartar A, Druilhe P & Gras-Masse H. Improved detection of human antibodies to a Plasmodium antigen using a peptide modified with Aib residues. (
  • As antibodies that fitted specific germs had been discovered, it was natural to think that they were built on a template of antigen. (
  • Armed with this revolutionary knowledge, Niels Jerne [7] realised that cells are factories that can swiftly convert DNA to RNA to polypeptide, and proposed the Selection Theory, postulating that antibodies are preformed in myriad diversity, awaiting contact with an antigen that fits (Figure 2). (
  • To assess the cellular source of infectious viruses derived from MDM, virus-containing media from infected cells were precipitated with specific antibodies. (
  • explains that so-called " autoantibodies " are merely antibodies generated in response to pathogenic bacterial cells that have been destroyed as a result of an active immune response - in essence, collateral damage. (
  • 1. Abramov V., Kosarev I., Motin V., Khlebnikov V., Vasilenko R., Sakulin V., Machulin A., Uversky V., Karlyshev A. Binding of LcrV protein from Yersinia pestis to human T-cells induces apoptosis, which is completely blocked by specific antibodies. (
  • We found immunization of HHDII-DR1 mice, which express human HLA-A2 and HLA-DR1, with pTVG-AR augmented AR LBD HLA-A2-restricted peptide-specific, cytotoxic immune responses in vivo that could lyse human prostate cancer cells. (
  • Using an HLA-A2-expressing autochthonous model of prostate cancer, immunization with pTVG-AR augmented HLA-A2-restricted immune responses that could lyse syngeneic prostate tumor cells and led to a decrease in tumor burden and an increase in overall survival of tumor-bearing animals. (
  • their activation is a crucial step in the induction of many immune and autoimmune responses. (
  • Single application of only low vector doses elicited strong and long-lasting cytotoxic T-cell responses, providing protective antiviral and antitumor immunity. (
  • However, there is a growing need not only to develop improved vaccines against such acute infections but also to generate therapeutic vaccines which can stimulate specific immune responses to persistent viruses such as the human immunodeficiency virus or the human hepatitis C virus ( 1 , 2 ). (
  • These actions can be further amplified by specific adaptive immune responses adapted to the activating stimulus. (
  • A good understanding of the mechanisms by which innate immune cell-derived EVs influence adaptive immune responses, or vice versa, may reveal novel insights in the regulation of the immune system and can open up new possibilities for EVs (or their components) in controlling immune responses, either as a therapy, target, or as an adjuvant in future immune modulating treatments. (
  • These accumulating new insights indicate that in contrast with the conventional idea that innate immune cells only participate in immune responses as terminal effector cells, they also significantly contribute to the initiation and shaping of adaptive immune responses. (
  • Naive CD4 + T cells were instructed by MPLA-tDCs to be hyporesponsive to antigen-specific restimulation and to suppress the induction of T helper cell type 1 and 17 responses. (
  • In conclusion, MPLA-tDCs are able to modulate antigen-specific responses of both naive and memory CD4 + T cells and might be a promising strategy to "turn off" self-reactive CD4 + effector T cells in autoimmunity. (
  • One of the main challenges in the field of autoimmunity is the attenuation of aberrant T cell immune responses to "self. (
  • tDCs exhibit a reduced costimulatory capacity and an anti-inflammatory cytokine secretion profile and are able to modulate CD4 + T cell responses ( 6 , 7 ). (
  • Major Histocompatibility Complex (MHC) glycoproteins are heterodimeric cell surface receptors that function to present antigen peptide fragments to T cells responsible for cell-mediated immune responses. (
  • The central event in the cel- mediated responses) or in both the afferent lular immune response to invading microor- and effector limbs of the immune response ganisms is the specific recognition of for- (T cell-mediated responses - e.g., delayed eign peptides bound to major histocompat- hypersensitivity). (
  • On the other hand, tumor and stem cell derived EVs have been identified to exert an inhibitory effect on immune responses by carrying immuno-modulatory effectors, such as transcriptional factors, non-coding RNA (Species), and cytokines. (
  • 3. BenMohamed L, Gras-Masse H, Tartar A, Daubersies P, Brahimi K, Bossus M, Thomas A & Druilhe P. Lipopeptide immunization without adjuvant induces potent and long-lasting B, T helper, and cytotoxic T lymphocyte responses against a malaria liver stage antigen in mice and chimpanzees. (
  • We provide evidence that endogenously produced activin-A suppresses antigen-specific Th2 responses and protects against airway hyperresponsiveness and allergic airway disease in mice. (
  • Importantly, we reveal that activin-A exerts suppressive function through induction of antigen-specific regulatory T cells that suppress Th2 responses in vitro and upon transfer in vivo. (
  • Evaluating CD8 + T Cell Responses In Vitro. (
  • Induction of tumor-specific CTL responses using the C-terminal fragment of Viral protein R as cell penetrating peptide. (
  • HLA-A*01:03, HLA-A*24:02, HLA-B*08:01, HLA-B*27:05, HLA-B*35:01, HLA-B*44:02, and HLA-C*07:01 monochain transgenic/H-2 class I null mice: novel versatile preclinical models of human T cell responses. (
  • M protein also contains moieties that similarly behave as such superantigens, thus further boosting immune responses to virulent strains ( 12 , 13 ) (see "vaccines" below). (
  • Thus, HIV escapes antiviral immune responses and eradication by the host's immune system. (
  • studied the selection pressure exerted by HLA-restricted immune responses on the evolution of the HIV-1 sequence at the population level ( 30 ). (
  • Human immunodeficiency trojan type 1 (HIV-1) mostly owes its success to its capability to evade web host immune responses. (
  • However, targeted immunotherapy using leukemia vaccines has been heavily investigated because these vaccines elicit specific immune responses against leukemia cells while sparing normal tissue. (
  • Vaccination with DNA- or peptide-based vaccines relies on T cell recognition, either in the afferent (T cell-dependent antibody-mediated responses) or in both the afferent and effector limbs of the immune response (T cell-mediated responses - e.g., delayed hypersensitivity). (
  • In most immunological systems, including post-infectious protective immune responses, only some peptides from a large number of potential candidates are actually the target of a vigorous immune response. (
  • Many efforts are made to find the target antigens may be included in an anti-cancer vaccine and to characterize their epitopes T. However, the observed responses are often inadequate and fail to recruit enough CD4 and CD8 T cells to eliminate tumors. (
  • We have in particular shown that the amplitude responses in T cell epitopes different depends on the size of the specific naive repertoire of these peptides. (
  • We asked whether the adaptive immune system can also affect the character and magnitude of innate inflammatory responses. (
  • Figure 6: Memory CD4 + T cells induce IIC responses independently of PAMP recognition. (
  • Iwasaki, A. & Medzhitov, R. Toll-like receptor control of the adaptive immune responses. (
  • Rogers, P.R., Dubey, C. & Swain, S.L. Qualitative changes accompany memory T cell generation: faster, more effective responses at lower doses of antigen. (
  • London, C.A., Lodge, M.P. & Abbas, A.K. Functional responses and costimulator dependence of memory CD4 + T cells. (
  • An unexpected antibody response to an engineered influenza virus modifies CD8 + T cell responses. (
  • Three Types of Functional Regulatory T Cells Control T Cell Responses at the Human Maternal-Fetal Interface. (
  • It is accepted that both helper and CTLs play a critical role in immune antitumor responses. (
  • Thus, the design of effective immune-based therapies for cancer relies in the identification of relevant tumor-associated antigens (TAAs) capable of eliciting strong helper and cytotoxic T-cell responses against tumor cells. (
  • VL - 60 IS - 18 N2 - It is accepted that both helper and CTLs play a critical role in immune antitumor responses. (
  • The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. (
  • Human in vitro and murine in vivo models of rotavirus infection were used to delineate the role of primary plasmacytoid DCs in initiating B cell responses. (
  • An effective tumor vaccine may be required to induce both CTLs and T-helper (Th) responses against tumor-associated antigens. (
  • CD4+ Th cells that recognize MHC class II-restricted epitopes play a central role in the initiation and maintenance of antitumor immune responses. (
  • Endothelial cells lining the blood vessels are principal players in vascular inflammatory responses. (
  • We report here that biosafe coronavirus-based vaccine vectors facilitate delivery of multiple antigens and immunostimulatory cytokines to professional antigen-presenting cells in vitro and in vivo . (
  • While peptide vaccines may bind directly to the MHC, recombinant vaccines must undergo proteolytic processing through the MHC class II pathway in endosomal vesicles, and expression products of DNA vaccines enter both the cytoplasmic/endoplasmic reticulum MHC class I pathway and can also be uptaken by professional antigen-presenting cells (2). (
  • Among the chemokine receptor genotypes, only the frequency of the CCR5-▵32 allele was significantly higher in LT-NP compared with the group of standard progressors. (
  • Our study suggests that the HLA DRB1*03 allele may explain a common etiology underlying the co-morbidity of Graves' disease, type 2 diabetes, and schizophrenia in our patient. (
  • While HLA-DR15 confers a markedly increased disease risk, the protective HLA-DR1 allele is dominantly protective in trans with HLA-DR15 (ref. 2). (
  • This disease is mainly a Th1 lymphocyte mediated aggression to melanocytes after a viral trigger in the presence of HLA-DRB1*0405 allele. (
  • 7 4 1 Over 27 million donors are now registered in the international database ( ) and an increasing proportion of these donors are typed by molecular techniques at all HLA loci and at the allele level. (
  • In fact, the null allele of the HLA-DRB4 gene ( DRB4*0103102N ) is transcribed, but it is an aberrant protein due to the lack of splicing out of the first exon 11 . (
  • The null allele DRB4*0103102N has been found on HLA-DRB1*04:01, *04:02 and *04:04 haplotypes 13;14 . (
  • The reference cell lines for this allele are DBB and JHO2821 15;16 . (
  • Molecular model of the alphabeta T cell receptor bound to the influenza haemagglutinin antigen and MHC class II molecule HLA-DR1. (
  • The image off to the side shows a piece of a poisonous bacterial protein (SEI peptide) bound within the binding cleft portion of the HLA-DR1 molecule. (
  • Once a T cell recognizes a peptide within an MHC class II molecule, it can stimulate B-cells that also recognize the same molecule in their B cell receptors. (
  • The MHC II molecule bound to a peptide is then transported to the cell membrane surface. (
  • In the instance of an infection, the peptide (such as the staphylococcal enterotoxin I peptide) is bound into a DR molecule and presented to a few of a great many T-cell receptors found on T-helper cells. (
  • Tetramers bind to T cell receptors (TCR) that recognize the MHC molecule/peptide combination with high specificity. (
  • The initial event required for entry is the interaction of the major viral envelope glycoprotein, gp350, with complement receptor type 2 molecule CD21, previously referred to as CR2 ( 27 , 33 ). (
  • What HLA molecule is it linked to? (
  • Uncovering the peptide-binding specificities of HLA-C: a general strategy to determine the specificity of any MHC class I molecule. (
  • Cytokine-induced expression of vascular cell adhesion molecule-1 (VCAM-1) by astrocytes and astrocytoma cell lines. (
  • from the HLA-DR molecule nearly doubled the half-life of HLA-DR1/course II-associated invariant-chain peptide complexes. (
  • All cell lines stained positive for both cytokeratins, the epithelial intermediate filaments, and the epithelial cell adhesion molecule E-cadherin, and they lacked markers of BM-derived cells. (
  • Antigén 16 je nízkoafinitný receptor pre IgG, antigén CD56 je identický s NCAM-1 (Neural Cellular Adhesion Molecule 1). (
  • Taken together, this novel vaccine platform is well suited to deliver antigens and immunostimulatory cytokines to DCs and to initiate and maintain protective immunity. (
  • Single immunization with only low doses of coronavirus-based vaccine vectors was sufficient to elicit (i) vigorous expansion and optimal differentiation of CD8 + T cells, (ii) protective and long-lasting antiviral immunity, and (iii) prophylactic and therapeutic tumor immunity. (
  • Moreover, the possible contribution of innate immune cell-derived extracellular vesicles (EVs) to the modulation of adaptive immunity will be outlined in this review. (
  • Mechanisms that are involved in the cross-talk between innate and adaptive immunity obviously include cell-cell contacts and the release of a diverse array of soluble factors, including cytokines and chemokines. (
  • An essential element determining the balance between immunity and tolerance is antigen recognition on the surface of antigen presenting cells (APC) by the T cell receptor (TCR) on T cells [ 10 - 19 ]. (
  • Still, its effects on T helper (Th) cell-mediated immunity, critical for allergic and autoimmune diseases, are elusive. (
  • Cell-mediated immunity to collagen and collagen alpha chains in rheumatoid arthritis and other rheumatic diseases. (
  • Macrophages (Mϕ) play a central role as effector cells in immunity to intracellular pathogens such as Mycobacterium . (
  • Here we report that this dual role may emanate from the functional plasticity of Mϕ: Whereas Mϕ-1 polarized in the presence of granulocyte-Mϕ colony-stimulating factor promoted type 1 immunity, Mϕ-2 polarized with Mϕ colony-stimulating factor subverted type 1 immunity and thus may promote immune escape and chronic infection. (
  • Type 1 cell-mediated immunity is required for granuloma formation and effective host defense against intracellular pathogens ( 1 ), but mycobacteria are able to escape immunity and persist in a nonreplicating state inside Mϕ for many years ( 2 ). (
  • The molecular and cellular mechanisms that underlie the development of effective immunity versus latent infection (or immune escape) and the induction of immunopathology after Mycobacterium tuberculosis infection, however, remain poorly understood. (
  • Activation of the innate immune system is the first step in the induction of immunity against weak tumor antigens. (
  • CD4 + T-cell memory: generation and multi-faceted roles for CD4 + T cells in protective immunity to influenza. (
  • Mixed signature of activation and dysfunction allows human decidual CD8 + T cells to provide both tolerance and immunity. (
  • The SCID mutation occurred on the CB17 strain, which has high levels of innate immunity, most notably natural killer (NK) cells, which eliminated a majority of the transferred foreign cells. (
  • Mycobacterium tuberculosis survives in macrophages in the face of acquired CD4 + T-cell immunity, which controls but does not eliminate the organism. (
  • In most healthy persons, acquired immunity, mediated by T cells, controls but does not eradicate M. tuberculosis infection, resulting in persistent bacilli within macrophages. (
  • Major histocompatibility complex type II (MHC-II)-restricted CD4 T cells play a key role in protective immunity to M. tuberculosis during primary infection as well as in containing persistent bacilli ( 18 , 24 , 25 , 31 , 33 ). (
  • Thus, the primary role of IFN-γ in human immunity to M. tuberculosis may lie in its ability to up-regulate MHC-II Ag processing for CD4 T cells. (
  • The N-terminal domain of the mature protein forms an alpha-helix that constitutes the exposed part of the binding groove, the C-terminal cytoplasmic region interact with the other chain forming a beta-sheet under the binding groove spanning to the cell membrane. (
  • This means HLA-DRB1 is rapidly evolving, much more rapidly than almost all other protein encoding loci. (
  • For this purpose, MPLA-tDCs were loaded with purified protein derivative (PPD) as antigen and co-cultured with autologous naive or memory CD4 + T cells. (
  • Many pathogens have evolved molecular mechanisms to escape recognition by the immune system by variation of antigenic protein sequences. (
  • The human TAP (transporter natural immune response is generated upon associated with antigen presentation) mole- immunization with the whole protein are cule selects peptides according to a binding called dominant epitopes. (
  • These include ipilimumab, which targets cytotoxic lymphocyte-associated protein 4 (CTLA-4), and nivolumab and pembrolizumab, which target programmed cell death protein 1 (PD-1). (
  • gp42 can interact with the HLA class II protein HLA-DR ( 32 ). (
  • To investigate the dependence of EBV infection on cellular receptors, a recombinant EBV reporter virus expressing enhanced green fluorescent protein (EGFP), designated EBfaV-GFP, has been constructed ( 30 ). (
  • Here, we use hemagglutinin and influenza A virus X31/A/Aichi/68 as examples to describe the key steps in identification of CD4+ T cell epitopes from a single antigenic protein and the entire genome of a pathogen, respectively. (
  • Interferon-gamma induces tyrosine phosphorylation of interferon-gamma receptor and regulated association of protein tyrosine kinases, Jak1 and Jak2, with its receptor. (
  • Induction of guanylate binding protein 5 by gamma interferon increases susceptibility to Salmonella enterica serovar Typhimurium-induced pyroptosis in RAW 264.7 cells. (
  • The protein encoded by this gene belongs to the HLA class II beta chain paralogues . (
  • PTPN22 is known formally as protein tyrosine phosphatase, non-receptor type 22. (
  • Ni reactivity is neither dependent on protein processing in antigen-presenting cells nor affected by the nature of HLA-DR-associated peptides. (
  • DNA vaccines are bacterial plasmids constructed to express an encoded protein following in vivo administration and subsequent cell transfection. (
  • The epitopes to which a natural immune response is generated upon immunization with the whole protein are called dominant epitopes. (
  • This fascinating process literally creates a representation, on the cell surface, of the protein pool contained within the cell, displayed as MHC-peptide complexes. (
  • Co-localization of the tumor-suppressor protein p53 and human papillomavirus E6 protein in human cervical carcinoma cell lines. (
  • Furthermore, T cells that reacted with peptide HER2(883) could also recognize antigen-presenting cells that process HER2/neu recombinant protein. (
  • We designed a novel recombinant protein comprised of the HLA-DRα1 domain linked to MOG-35-55 peptide but lacking the β1 domain found in pMHC and treated MCAO after 4 h reperfusion in humanized DR2 mice. (
  • This study determined that the 19-kDa lipoprotein from M. tuberculosis inhibits IFN-γ-regulated HLA-DR protein and mRNA expression in human macrophages. (
  • Inhibition of HLA-DR expression was associated with decreased processing and presentation of soluble protein Ags and M. tuberculosis bacilli to MHC-II-restricted T cells. (
  • IFN-γ activates antimicrobial mechanisms of macrophages and regulates MHC-II antigen (Ag) processing by up-regulating MHC-II mRNA and protein expression ( 5 ). (
  • HLA (human leukocyte antigens) were originally defined as cell surface antigens that mediate graft-versus-host disease. (
  • The MHC in humans is called Human Leukocyte Antigens (HLA). (
  • Promiscuous T-cell epitopes that can be presented by multiple human leukocyte antigens (HLAs) are prime targets for vaccine and immunotherapy development because they are effective in a high proportion of the human population. (
  • However, it is now more and more recognized that both at inflammatory sites and in secondary lymphoid structures, DCs can interact with innate immune cells (i.e., mast cells, neutrophils, macrophages, eosinophils, basophils, and natural killer (NK) cells) resulting in the modulation of DC migration and function. (
  • Recent studies have exhibited that immune complexes made up of ACPA are capable of inducing inflammation, by activating macrophages through cell surface Fc receptors (7, 8). (
  • Nevertheless, no prior research have demonstrated the power of a particular potential endogenous TLR ligands within RA SF to activate macrophages and HEK293 cells through TLR2 or TLR4. (
  • Leprosy The dense subepithelial mononuclear infiltrate in oral lichen planus is composed of T cells and macrophages, and there are increased numbers of intraepithelial T cells. (
  • Although the precise pathogenesis of RA remains unclear, T cells, B cells, macrophages, neutrophils and synovial fibroblasts are central to the mechanisms of joint inflammation and disease progression. (
  • Although human immunodeficiency virus type 1 (HIV-1) is generally thought to assemble at the plasma membrane of infected cells, virions have been observed in intracellular compartments in macrophages. (
  • Our data indicate that most of the infectious HIV produced by primary macrophages is assembled on late endocytic membranes and acquires antigens characteristic of this compartment. (
  • Nontheless, T cells with indirect allospecificity can contribute to graft rejection by activating macrophages, which cause tissue injury and fibrosis, and are also likely to be important in the development of an alloantibody response to graft. (
  • Gamma interferon (IFN-γ) has a central role in host defenses against M. tuberculosis by activating macrophages and regulating major histocompatibility complex class II (MHC-II) antigen (Ag) processing. (
  • Thus, M. tuberculosis , through 19-kDa lipoprotein activation of TLR-2, inhibits IFN-γR signaling in human macrophages, resulting in decreased MHC-II Ag processing and recognition by MHC-II-restricted CD4 T cells. (
  • Inhibition of IFN-γ-regulated processing of mycobacterial Ags for CD4 T cells provides a mechanism for M. tuberculosis to escape detection and persist within macrophages. (
  • M. tuberculosis activates macrophages via Toll-like receptors (TLRs). (
  • A flexible docking approach for prediction of T cell receptor-peptide-MHC complexes. (
  • 1999. Role of the T cell receptor α-chain in stabilising TCR-Superantigen-MHC class II complexes. (
  • We have used T cells bearing TCRs that are closely related in sequence as probes to detect conformational variants of peptide-MHC complexes in murine experimental autoimmune encephalomyelitis in H-2 u mice. (
  • Insect cell expression of recombinant I-A u with covalently tethered class II-associated invariant chain peptide or other peptides which bind relatively weakly, followed by proteolytic cleavage of the peptide linker and replacement by MBP1-9[4Y] in vitro, results in complexes that resemble peptide-pulsed PL-8 cells. (
  • They are also of particular importance for the effective use of multimeric peptide-MHC complexes to characterize the properties of Ag-specific T cells. (
  • These "mature" peptide-MHC (pMHC) complexes are subsequently transported to the cell surface by either vesicular transport ( 11 ) or secreted as exosomes ( 12 ). (
  • Upon binding of the TCR to cognate peptide-MHC complexes presented on the surface of antigen presenting cells (APCs), a specialized supramolecular structure known as the immunological synapse (IS) assembles at the T cell-APC interface. (
  • HLA-B7-restricted islet epitopes are differentially recognized in type 1 diabetic children and adults and form weak peptide-HLA complexes. (
  • HIV particles budding at the cell surface would need to recruit these so-called ESCRT complexes to the plasma membrane, whereas the presence of the ESCRT complexes on endosomes may favor intracellular virus assembly. (
  • These data indicate that labile, nonactivating complexes between the SE9 TCR and most HLA-DR/peptide conjugates might supply sterically optimized coordination sites for Ni ions, three of which were identified in this study. (
  • Again, it is important to understand that these MHC-peptide complexes are "fully visible" on the cell surface, from outside the cells. (
  • Who's looking and why are these MHC-peptide molecular complexes so important for transplant compatibility and more in general, the immune response, including defense against infections and cancer? (
  • The above-mentioned process of MHC-peptides complexes exposure on the outer membranes happens virtually in all human cells (except erythrocytes - red blood cells). (
  • Thus, the αβ T cell repertoire could be characterized by analyzing αβ heterodimers on T cells or identifying recognized peptide-MHC complexes on antigen presenting cells. (
  • Using a retroviral expression system encoding Foxp3 and HLA-DR1 covalently linked to the immunodominant peptide of the autoantigen type II collagen (DR1-CII), naive T cells were engineered to become regulatory T cells that express DR1-CII complexes on their surface. (
  • Progress into the understanding of immunopathology in rheumatoid arthritis is reviewed in the present article with regard to pro-inflammatory cytokine production, cell activation and recruitment, and osteoclastogenesis. (
  • Studies highlight the potential importance of T helper 17 cells and regulatory T cells in driving and suppressing inflammation in rheumatoid arthritis, respectively, and highlight other potential T-cell therapeutic targets. (
  • Peripheral blood mononuclear cells from patients with rheumatoid arthritis, gout, ankylosing spondylitis and degenerative joint disease were cultured in the presence of native types I, II and III collagens and alpha chains from each of these types of collagen. (
  • Most patients with rheumatoid arthritis (RA) express HLA-DR4, HLA-DR1 or HLA-DR10. (
  • This study was performed to systematically summarize results on the association of HLA-DRB1 with rheumatoid arthritis (RA) in China. (
  • TCR gene usage in the response to HA/HLA-DR appears to conserve charged interactions between three lysines of the peptide and acidic residues on the TCR. (
  • The HLA gene complex resides on a 3 Mbp stretch within chromosome 6p 21. (
  • The HLA-DRB1 locus is ubiquitous and encodes a very large number of functionally variable gene products (HLA-DR1 to HLA-DR17). (
  • Symposium "The Third Revolution cells must be taken into account when designing new generation on Vaccines: DNA Vaccines", peptide- or gene-based vaccines. (
  • Other genetic factors, namely an SDF1 chemokine gene variant SDF1-3′A, which is the ligand for the CXCR4 chemokine receptor, conferred a recessive protective effect in long-term nonprogressors (LT-NP). (
  • The HLA gene complex resides on a 3 Mbp stretch within chromosome 6, p-arm at 21.3. (
  • Twenty-six different gene transcripts were measured quantitatively in peripheral blood mononuclear cells (PBMC) before and after therapy, and correlated with clinical, virological, and histological data. (
  • Thus, the immunobiology of antigen recognition by T cells must be taken into account when designing new generation peptide- or gene-based vaccines. (
  • However, the rheumatoid T-cell repertoire is not entirely under HLA-DR influence, as demonstrated by discrepancies in VB JB gene usage between identical twins discordant for RA and by contraction of the CD4 αβ T-cell repertoire in RA patients. (
  • The hurdles of NK activity and accelerated lymphomagenesis were recently overcome in three new strains: NOD/Shi- scid IL2r γ null ( 8 , 9 ), NOD- scid IL2r γ null ( 10 , 11 ), and BALB/c- Rag2 null IL2rγ null ( 12 ), which all lack the IL-2 family common cytokine receptor γ chain gene ( IL2rg ). (
  • CD8αα + T cells located at the DEJ lack chemokine-receptor expression required for lymphocyte egress and recirculation, express gene signatures of T-cell activation and antiviral activity, and produce cytolytic granules during clinical and virological quiescent time periods. (
  • HLA-DR53 is not expressed on the HLA-B57DR7Dw11DQ9 (DQA1*02:01, DQB1*03:03) haplotype (as in the cell line DBB (IHW 9052) representing the conserved extended haplotype (CEH) 57.1) due to a base substitution at the 3' end of the first intron of the gene 9;10 . (
  • The gene encoding the HLA-DR53 antigen is HLA-DRB4 which exists only on DRB1*04, *07 and *09 haplotypes. (
  • HLA-A*0201/DRB1*0101 transgenic mice (A2/DR1 mice) have been developed to study the immunogenicity of tumor antigen-derived T cell epitopes. (
  • To evaluate the immunogenicity of tumor antigen-derived T cell epitopes in vivo , various HLA class I or HLA class II transgenic mouse models have been developed [ 1 - 5 ]. (
  • Among these mouse models, Lemonnier laboratory has created the new generation of humanized HLA-transgenic mice like the HLA-A*0201/DRB1*0101 (A2/DR1) mouse model. (
  • We show that autoreactive α3 -specific T cells expand in patients with Goodpasture disease and, in α3 -immunized HLA-DR15 transgenic mice, α3 -specific T cells infiltrate the kidney and mice develop Goodpasture disease. (
  • HLA-DR15-α3 tetramer T cells in HLA-DR15 transgenic mice exhibit a conventional T-cell phenotype (T ) that secretes pro-inflammatory cytokines. (
  • In contrast, HLA-DR1-α3 tetramer T cells in HLA-DR1 and HLA-DR15/DR1 transgenic mice are predominantly CD4 Foxp3 regulatory T cells (T cells) expressing tolerogenic cytokines. (
  • HLA-DR1-induced T cells confer resistance to disease in HLA-DR15/DR1 transgenic mice. (
  • Starting at an early age, these transgenic mice developed spontaneous immune disorders mimicking human autoimmune lymphoproliferative syndrome with distinct manifestations, including enlarged spleens and lymph nodes, inflammatory infiltration in the livers and lungs, increased levels of double-negative T cells in peripheral blood, and increased serum IgG levels. (
  • While studying the latter, we raised a T-cell line from the thymus of a myasthenia gravis patient against recombinant α subunit of the human acetylcholine receptor, the target of this autoimmune disease. (
  • Furthermore, human DCs transduced with Melan-A-recombinant human coronavirus 229E efficiently activated tumor-specific CD8 + T cells. (
  • Moreover, highly efficient antigen delivery to human DCs with recombinant human coronavirus 229E and specific stimulation of human CD8 + T cells revealed that this approach is exceptionally well suited for translation into human vaccine studies. (
  • The HLA-DRB3 locus encodes the HLA-DR52 specificity, is moderately variable and is variably associated with certain HLA-DRB1 types. (
  • The HLA-DRB4 locus encodes the HLA-DR53 specificity, has some variation, and is associated with certain HLA-DRB1 types. (
  • The HLA-DRB5 locus encodes the HLA-DR51 specificity, which is typically invariable, and is linked to the HLA-DR2 types. (
  • Because T cell epitopes determine the specificity of a T cell immune response, their prediction and identification are important steps in developing peptide-based vaccines and immunotherapies. (
  • The specificity of this HLA-DR-promiscuous VA22/VB17 + TCR is primarily harbored in its α chain. (
  • They have many advantages including specificity but have the risk of immunogenicity is to say, the risk of eliciting an immune response. (
  • All the SARC-L1-derived cell lines induced aggressive subcutaneous tumors in A2DR1 mice in vivo . (
  • NSG mice humanized with allergen-specific T-cell lines as in vivo model of respiratory allergy. (
  • These vectors selectively targeted DCs in vitro and in vivo resulting in vector-mediated antigen expression and efficient maturation of DCs. (
  • T cells that can distinguish these two conformers can also be generated by the immunization of H-2 u mice, indicating that differential recognition of the conformers is observed for responding T cells in vivo. (
  • An optimized antigen-presenting cell (APC) for tumor immunotherapy should produce a strong antigen specific cytotoxic T cell (CTL) response to tumor-associated antigens which can persist in vivo and expand on antigen re-encounter. (
  • While ligelizumab shows superior inhibition of IgE binding to Fc?RI, basophil activation, IgE production by B cells and passive systemic anaphylaxis in an in vivo mouse model, ligelizumab is less potent in inhibiting IgE:CD23 interactions than omalizumab. (
  • 2. The method of claim 1 wherein said method is carried out in vivo, said antigent-presenting cells are provided endogenously and said aqueous culture medium is endogenous blood or lymph. (
  • Bradley, L.M., Duncan, D.D., Yoshimoto, K. & Swain, S.L. Memory effectors: a potent, IL-4-secreting helper T cell population that develops in vivo after restimulation with antigen. (
  • Others classify lichen planus as a cell-mediated immune response and believe that since a specific antigen has not been identified, it is premature to classify the disorder as autoimmune. (
  • In this report, we evaluated the immune and anti-tumor efficacy of a DNA vaccine targeting the AR LBD (pTVG-AR) in relevant rodent preclinical models. (
  • These data show that the AR is as a prostate cancer immunological target antigen and that a DNA vaccine targeting the AR LBD is an attractive candidate for clinical evaluation. (
  • A major challenge to natural or vaccine-induced immune control of HIV is the ability of the virus to mutate rapidly when it comes under pressure from the host's immune system ( 4 , 8 , 15 , 26 ). (
  • Myeloid leukemia vaccines are most likely beneficial for eradicating minimal residual disease after chemotherapy or targeted therapy [ 6 ] although the suppressed immune status of patients who receive these treatments may influence their vaccine response. (
  • Molecular identification of tumor rejection antigen has helped define several classes of antigen. (
  • These studies have relevance to understanding the molecular details of T cell recognition in murine experimental autoimmune encephalomyelitis. (
  • Discrepancy in literature may be due to stem cell culture conditions, methods of EV purification, EV molecular content, and functional state of both parental and target cells. (
  • We present by far the largest set of Molecular Dynamics simulations investigating the effects of T-cell receptor binding on the dynamics of peptide/MHC. (
  • The development of HLA molecular typing technologies and the availability of more than 27 million donors in the international database has greatly facilitated unrelated donor searches. (
  • High-density mapping of the MHC identifies a shared role for HLA-DRB1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis. (
  • There is a high level of allelic diversity at HLA DRB1, it is second only to HLA-B locus in number of allelic variants. (
  • The genetic investigation revealed that the patient carried the HLA DRB1*03-HLA DQB1*02 haplotype. (
  • We suppose that HLA DRB1*03 may be the common cause of these three simultaneous diseases. (
  • We describe new HLA-associated mutations in both viral protease and RT, several of which are associated with HLA-DRB1. (
  • These include HLA-DRB1 * 0401, * 0404, * 0405 and * 0408 (identified by serology as HLA-DR4), HLA-DRB1 * 0101 and * 0102 (HLA-DR1), and HLA-DRB1*1001 (HLA-DR10). (
  • The gold standard is high resolution typing at the HLA-A, -B, -C, -DRB1, and -DQB1 loci (10/10 match). (
  • Single disparities for HLA-A, -B, - C, or -DRB1 are associated with increased risk of post-transplant complications, but less so in patients with advanced disease, and in those undergoing T-cell-depleted allografting. (
  • HLA-DQB1 mismatches seem to be better tolerated and some HLA-C, -DRB1 and -DPB1 disparities are potentially less immunogenic. (
  • It was found that HLA-DRB1*04, *0401, *0404, *0405 and *0410 are risk factors for RA in Chinese populations. (
  • Many studies have attempted to clarify the relationship between HLA-DRB1 and RA, but there has been no definite consensus to date in Chinese populations. (
  • Well-designed meta-analyses of Caucasian and American populations showed that there was a strong association between HLA-DRB1 and RA susceptibility and severity [ 5 ]. (
  • This is exemplified by the association of DRB1*04:01 with either DRB4*01:01:101 or DRB4*01:03:101 (as in the cell lines BOLETH and SUD). (
  • As exemplified in the cell lines BOLETH and BSM , the DRB4 may differ on the CEH 62.1 despite identity at DRB1 and DQB1. (
  • T cells engage these peptide-MHCs using T cell receptors (TCRs). (
  • In this study we used site directed mutagenesis and computational simulations to estimate the contribution of HLA-A2 side-chains to the binding of four different TCRs. (
  • Our results show that these TCRs have very different energetic 'footprints' on HLA-A2. (
  • The "second memory" is the adaptive immune system, which is cumulative information about dangerous microorganisms with which the individual interacts and through this interaction acquires the ability to defend itself from subsequent exposure with high efficiency. (
  • While most immunotherapies for cancer have focused on eliciting specific CD8+ cytotoxic T lymphocyte killing of tumor cells, a mounting body of evidence suggests that stimulation of anti-tumor CD4+ T cell help may be required for highly effective therapy. (
  • This clinical course and the pathologic findings support the hypothesis that the Castleman disease-associated tumor cells are the source of the anti-GBM autoantibodies. (
  • It is, therefore, important to establish suitable models that allow the in-depth characterization of disseminated tumor cells present at low frequencies of 10 −5 -10 −6 nucleated BM cells. (
  • On the other hand, the direct study of micrometastatic tumor cells has been hampered for many years by the lack of suitable markers to identify these cells in secondary organs. (
  • For patients with epithelial tumors, which represent the majority of cancers in industrialized countries, the detection level of micrometastatic tumor cells is now improved. (
  • Immunocytochemical screening with mAbs 3 against CKs now appears to be a reliable method to detect isolated tumor cells in BM. (
  • One explanation for this surprising finding is that BM might function as an important reservoir for disseminated epithelial tumor cells, which can be the source for further dissemination into other organs. (
  • Since tumor antigens were discovered, many clinical trials attempt to induce a cellular immune response that selectively targets tumor cells and spare the normal cells. (
  • Some new work has proposed that antigens longer than 10 amino acids, 11-14 amino acids, can be presented on MHC I eliciting a cytotoxic T cell response. (
  • Several cytotoxic T-cell epitopes for HER2/neu have been identified that enable the design of peptide-based therapeutic vaccines for tumors expressing this TAA. (
  • The cytokine environment influence on human skin-derived T cells. (
  • We detected that memory CD4 + T cells primed by MPLA-tDCs presented reduced proliferation and proinflammatory cytokine expression in response to PPD and were refractory to subsequent stimulation. (
  • Twenty-six different cytokine transcripts were measured quantitatively in peripheral blood mononuclear cells (PBMC) before and after therapy and correlated with therapy outcome as well as with clinical and liver histological data. (
  • The IFN gamma receptor: a paradigm for cytokine receptor signaling. (
  • Mononuclear phagocytes including Mϕ are activated through ligation of pattern-recognition receptors such as Toll-like receptors (TLRs) by microbial ligands ( 3 , 4 ), which is generally considered to potentiate the production of the type 1 cytokine IL-12. (
  • IFN-γ, in turn, activates Mϕ and enhances cytokine secretion, antigen presentation and, supposedly, the bactericidal activity of Mϕ ( 6 ). (
  • Infarct volumes were quantified after 96 h reperfusion and immune cells from the periphery and CNS were evaluated for expression of CD74 and other cell surface, cytokine and pathway markers. (
  • This section includes, but is not limited to, studies looking at cytokines and cytokine receptors in allergy, eosinophils, mast cells, chemokines and their receptors, as well as specific diseases and their therapy. (
  • When a foreign pathogen enters the body, specific cells called antigen-presenting cells (APCs) engulf the pathogen through a process called phagocytosis . (
  • A hairpin turn in a class II MHC-bound peptide orients residues outside the binding groove for T cell recognition. (
  • HLAs corresponding to MHC class I ( A , B , and C ) present peptides from inside the cell. (
  • [ citation needed ] Foreign antigens presented by MHC class I attract killer T-cells (also called CD8 positive- or cytotoxic T-cells) that destroy cells. (
  • These cells have receptors that are similar to B cell receptors, and each cell recognizes only a few class II-peptide combinations. (
  • HLA-DR is an MHC class II cell surface receptor encoded by the human leukocyte antigen complex on chromosome 6 region 6p21.31. (
  • Maximum HLA heterozygosity of class I loci ( A , B , and C ) delayed acquired immunodeficiency syndrome (AIDS) onset among patients infected with human immunodeficiency virus-type 1 (HIV-1), whereas individuals who were homozygous for one or more loci progressed rapidly to AIDS and death. (
  • This unit describes procedures for labeling CD8 + T cells with MHC class I tetramers and CD4 + T cells with MHC class II tetramers. (
  • Efficient detection and immunomagnetic sorting of specific T cells using multimers of MHC class I and peptide with reduced CD8 binding. (
  • The relationship of MHC‐peptide binding and T cell activation probed using chemically defined MHC class II oligomers. (
  • MHC class II receptors display antigens for recognition by helper T cells (stimulate development of B cell clones) and inflammatory T cells (cause the release of lymphokines that attract other cells to site of infection) ( PUBMED:15120183 ). (
  • MHC class II moleculesthereby are critical for the initiation of the antigen-specific immuneresponse. (
  • Combination of HLA class I (HLA-A1, HLA-A2, HLA-B14, HLA-B17, HLA-B27) and class II antigens (HLA-DR5 and HLA-DR6) have been correlated with low rates of disease progression. (
  • In this report, we studied chemokine receptors (CCR2, CCR5), chemokine (SDF1), and HLA class I and II genotypes in LT-NP and attempted to find out whether any particular pattern of host genetics could be implicated in the LT-NP phenotype. (
  • This article will draw particular attention to an increasingly utilized class of anticancer drugs, the immune checkpoint inhibitors. (
  • Both the full-length form and the secreted gp42 form bind to gH/gL and HLA class II, and the functional significance of gp42 cleavage is not completely clear. (
  • Although the crystal structures of gp42 alone and gp42/HLA class II complex have been solved ( 15 , 19 ), the N-terminal region of gp42 (bound to gH/gL) is not visible in the structures, most likely due to its flexibility. (
  • Different classes have different functions: HLAs corresponding to MHC class I (A, B, and C), all of which are the HLA Class1 group, present peptides from inside the cell. (
  • however, the success of these methods has been limited for MHC class II (MHCII) due to the structural complexity of MHCII antigen presentation. (
  • The viral transcription group determines the HLA class I cellular immune response against human respiratory syncytial virus. (
  • Therefore, early in the formation of oral lichen planus lesions, CD8+ T cells may recognize an antigen associated with the major histocompatibility complex (MHC) class I on keratinocytes. (
  • The HLA complex is divided into three regions: class I, II, and III regions as first proposed by Jan Klein in 1977 57 . (
  • The classical HLA antigens encoded in each region are HLA-A, -B, and -C in the class I region, and HLA-DR, -DQ and -DP in the class II region. (
  • HLA class I and II antigens are partially co-clustered in the plasma membrane of human lymphoblastoid cells. (
  • Figure 5: Cognate recognition of antigen on MHC class II-expressing CD11c + cells is sufficient to induce IIC upregulation. (
  • TY - JOUR T1 - Defining promiscuous MHC class II helper T-cell epitopes for the HER2/neu tumor antigen. (
  • Innate immune cells are recognized for their rapid and critical contribution to the body's first line of defense against invading pathogens and harmful agents. (
  • Plaque-type psoriasis is a chronic inflammatory skin disease involving both the innate and the adaptive immune compartments, crosstalking with skin tissue cells. (
  • They have been shown to control natural killer cell activity and to suppress the innate immune response (IIR). (
  • A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis. (
  • We found that the response of memory, but not naive, CD4 + T cells enhances production of multiple innate inflammatory cytokines and chemokines (IICs) in the lung and that, during influenza infection, this leads to early control of virus. (
  • This represents a previously undescribed mechanism by which memory CD4 + T cells induce an early innate response that enhances immune protection against pathogens. (
  • Janeway, C.A. Jr. & Medzhitov, R. Innate immune recognition. (
  • Transcriptome analysis reveals similarities between human blood CD3 - CD56 bright cells and mouse CD127 + innate lymphoid cells. (
  • A nuclear receptor located throughout the body that plays a key role in the innate immune response. (
  • The complex interactions between the innate and adaptive immune systems are largely indeterminate - they have evolved over eons, and many of the interactions make no sense when looked at individually. (
  • The limited engraftment was due in part to the rejection of the cells by the host innate immune response. (
  • The authors hypothesized whether regulatory T (T reg) cells are required to restrain NK cells, the third lymphocyte lineage, whose features combine innate and adaptive immune cell properties. (
  • The gain of knowledge on the immune mechanisms that are induced by alum and other adjuvants that will be obtained from the proposed project, may lead to more effective vaccines, especially in allergen-specific immunotherapy, which have to be applied repeatedly over several years and mainly contain alum as adjuvant. (
  • The mechanisms by which tDCs exert their modulatory activity on autoreactive T cells include clonal deletion, anergy induction, or cell reprograming. (
  • This review aims to provide a comprehensive overview on the immune-mediated mechanisms characterizing the current pathogenic model of psoriasis. (
  • In the last three decades, the pathogenic model for psoriasis has been profoundly revised according to a broader and deeper understanding of the immune mechanisms leading to plaque formation. (
  • Here, we discuss recent literature on the regulation and assembly of IS and the mechanisms evolved by tumors to modulate its function to escape T cell cytotoxicity, as well as novel strategies targeting the IS for therapy. (
  • A type of amoeba in these groups differentiated and facilitated the process of detoxification through immunological mechanisms and became what is called a sentinel (S-cell) [ 1 ]. (
  • However, the mechanisms underpinning such HLA-mediated effects on self-tolerance remain unclear. (
  • Ongoing research projects include studies of paramyxovirus and herpesvirus entry mechanisms, IgE-receptor structure and function and TGF-beta ligand signaling pathways. (
  • However, translating the reconstitution of immune tolerance into the clinical setting is a daunting challenge fraught with the complexities of multiple interacting mechanisms overlaid on a background of variation in disease. (
  • Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. (
  • They are then displayed by the antigen-presenting cells to CD4+ helper T cells , [3] which then produce a variety of effects to eliminate the pathogen. (
  • Whereas Mϕ-1 efficiently stimulated type 1 helper cells, Mϕ-2 only poorly supported type 1 helper function. (
  • IL-12 is a heterodimer of p40 and p35 that drives polarization of naive T cells toward type 1 helper (Th1) cells and induces the release of IFN-γ from T and natural killer cells ( 5 ). (
  • Memory CD4 + T cell-induced IICs and viral control require cognate antigen recognition and are optimal when memory cells are either T helper type 1 (T H 1) or T H 17 polarized but are independent of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) production and do not require activation of conserved pathogen recognition pathways. (
  • Mice with a DC deletion in Irf4 displayed reduced numbers of intestinal interleukin 17-secreting helper T 17 (Th17) cells and failed to support Th17 cell differentiation in draining mesenteric lymph nodes following immunization. (
  • By concurrently analyzing T-regulatory and T-effector cells, they showed strong functional correlation between these subsets in healthy individuals and, strikingly, that alterations of this balance are associated with T helper type 2-mediated disease in a lymphopenic setting. (
  • Twenty-four hours after infection, cells were analyzed for EGFP fluorescence by flow cytometry using a FacsCalibur (Becton Dickinson). (
  • The aim of this study was to assess common phenotypic features of nine tumor cell lines established from BM of patients with cancer of the prostate (four cell lines), breast (two cell lines), lung (two cell lines), and colon (one cell line) using immunocytochemistry, flow cytometry, and reverse transcription-PCR. (
  • Chemokines and their cognate receptors play important role in the control of leukocyte chemotaxis, HIV entry and other inflammatory diseases. (
  • A crucial event determining the recognition and elimination of detrimental cells is antigen recognition by the T cell receptor (TCR) expressed on the surface of T cells. (
  • The autoimmune disease theory has yet to present a satisfactory reason, evolutionary or otherwise, why an immune system would attack human tissue. (
  • HLA-DR beta-chain polymorphism. (
  • The HLA-DRB4 promoter polymorphism is associated with differential expression of this locus 4 and this occurs at the level of mRNA production 3 . (
  • The influence of HLA on thymidine analogue mutation pathways was not observed. (
  • After transplantation of organ allografts, there are two pathways of antigen presentation. (
  • There has been a rapid surge in clinical trials involving stem cell therapies over the last two to three years and those trials are establishing the clinical pathways for an emergent new medicine. (
  • This includes bone and cartilage repair, cell types into which MSCs readily differentiate, and immune conditions such as graft versus host disease and autoimmune conditions that utilize the MSC's immune suppressive properties. (
  • Membrane fusion requires the additional interaction between virion gp42 and cellular HLA-DR. This binding is thought to catalyze membrane fusion through a further association with the gp85-gp25 (gH-gL) complex. (
  • Virion penetration of the B-cell membrane requires the additional interaction of the ternary EBV glycoprotein gp85-gp25-gp42 complex with its cellular ligand ( 20 , 35 ). (
  • The interaction between the TCR and antigenic peptide in complex with MHCs is a crucial step in T cell activation. (
  • Stoichiometry of interaction between interferon gamma and its receptor. (
  • Abatacept inhibits activation of T cells by blocking the interaction between CD28 on T cells and B7 on antigen-presenting cells. (
  • Optimal inhibition of X4 HIV isolates by the CXC chemokine stromal cell-derived factor 1 alpha requires interaction with cell surface heparan sulfate proteoglycans. (
  • Angiotensin-converting Enzyme 2 (ACE2)-CHO Cell Line Model for COVID-19: Helps researchers to further study the interaction between the receptor ACE2 and the COVID-19 virus. (
  • Such profound functional consequences for T-cell recognition as we report here may explain this example of conserved major histocompatibility complex diversity. (
  • H. Zhang, H. Lim, B. Knapp , C. M. Deane, M. Aleksic and P. A. van der Merwe C . The contribution of major histocompatibility complex contacts to the affinity and kinetics of T cell receptor binding. (
  • In spite of high frequencies of metal allergies, the structural basis for major histocompatibility complex (MHC)-restricted metal recognition is among the unanswered questions in the field of T cell activation. (
  • These cells then bind to antigens on the surface of B-cells stimulating B-cell proliferation. (
  • Additionally, tDCs are able to promote the differentiation and proliferation of T cells with regulatory functions (Treg) ( 8 ). (
  • Various triggers, including recently identified autoantigens, Toll-like receptor agonists, chemerin, and thymic stromal lymphopoietin may activate the pathogenic cascade resulting in enhanced production of pro-inflammatory and proliferation-inducing mediators such as interleukin (IL)-17, tumor necrosis factor (TNF)-α, IL-23, IL-22, interferon (IFN)-α, and IFN-γ by immune cells. (
  • Before the late 1990s, there was a debate on whether KC proliferation was due to intrinsic KC defects triggering an immune response or, viceversa, whether KC hyperproliferation was a secondary phenomenon induced by immune activation and inflammation. (
  • 3. The method of claim 1 wherein said method is carried out in vitro, and said stimulation is determined by an assay selected from the group consisting of (i) T cell proliferation, (ii) interleukin-2 secretion, (iii) interferon-gamma secretion, (iv) granulocyte macrophage-colony stimulating factor secretion and (v) cytotoxicity. (
  • HLA-DR is an αβ heterodimer, cell surface receptor, each subunit of which contains two extracellular domains, a membrane-spanning domain and a cytoplasmic tail. (
  • They are commonly heterogeneous in size ranging from 50 to 1000 nm in diameter depending on the state of the cell during release by either direct shedding or budding from the plasma membrane (Figure 1 ). (
  • Exosomes, on the other hand, are generated through an invagination process of the endosomal membrane of multi-vesicular bodies (MVBs) found within the cells forming vesicles. (
  • Epstein-Barr virus (EBV) requires at a minimum membrane-associated glycoproteins gB, gH, and gL for entry into host cells. (
  • The presence of soluble gp42 inhibits membrane fusion with epithelial cells by forming a stable heterotrimer of gH/gL/gp42. (
  • EBV is an enveloped virus which contains a number of membrane glycoproteins required for membrane fusion and viral entry into the host cell. (
  • EBV gp42 has been shown to play an essential role in membrane fusion with B cells ( 7 , 16 , 17 ). (
  • Interestingly, EBV gp42 occurs in two forms in infected cells, a full-length membrane-bound form and a soluble form generated by proteolytic cleavage that is secreted from infected cells due to loss of the N-terminal transmembrane domain ( 21 ). (
  • However, membrane fusion with epithelial cells is inhibited by the presence of gp42 for both virus infection and cell-cell fusion ( 14 , 29 ). (
  • This is likely due to the formation of a heterotrimeric gH/gL/gp42 complex that is unable to mediate membrane fusion with epithelial cells, possibly due to steric hindrance of gH/gL receptor binding ( 3 , 11 ). (
  • 3 - 6 Two studies have demonstrated a statistically significant higher phenotype frequency of human leukocyte antigen (HLA) in ED patients than in healthy controls 7 and have identified the presence of inflammatory cells in the epiretinal membrane of patients with ED (Badrinath SS, et al. (
  • They are synthesised in the Endoplasmic Reticulum of cells, an intracellular system of membrane vescicles, where they fold, assuming their final tridimensional structure and then travel to the outer cell membrane where they end up exposed on the exterior part of the membrane, so as to be "visible" from the outside of cells. (
  • Defining the architecture of the red blood cell membrane: newer biophysical approaches. (
  • Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer and thus is a potential target for prostate cancer immunotherapy. (
  • Cell membrane labeling of Eimeria tenella sporozoites with the fluorescent dye PKH-67 GL for tracking parasite-host interactions. (
  • The hypothesis of overdominant selection (heterozygote advantage) at the MHC proposes that individuals heterozygous at HLA loci are able to present a greater variety of antigenic peptides than are homozygotes, resulting in a more productive immune response to a diverse array of pathogens ( 6 ). (
  • Contrasting roles of interallelic recombination at the HLA-A and HLA-B loci. (
  • A cohort of 473 HIV-1-infected patients was genotyped for the HLA-A and HLA-B loci. (
  • The definition of 'HLA matching' depends on the level of resolution and on which loci are tested. (
  • HLA typing by next-generation sequencing methods is likely to change matching algorithms by providing full sequence information on all HLA loci in a single step. (
  • The chapter talks about binding to the t-cell receptor, formation of the trimeric complex for signal transduction, and other structural features and idiosyncrasies. (
  • The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. (
  • The complex of HLA-DR (Human Leukocyte Antigen - DR isotype ) and peptide, generally between 9 and 30 amino acids in length, constitutes a ligand for the T-cell receptor (TCR). (
  • The genetics of HLA-DR is complex. (
  • B. Knapp C , C. M. Deane: T-cell receptor binding effects the dynamics of the peptide/MHC complex. (
  • Preassembly and ligand-induced restructuring of the chains of the IFN-gamma receptor complex: the roles of Jak kinases, Stat1 and the receptor chains. (
  • Seeing the light: preassembly and ligand-induced changes of the interferon gamma receptor complex in cells. (
  • Interferon gamma-induced transcription of the high-affinity Fc receptor for IgG requires assembly of a complex that includes the 91-kDa subunit of transcription factor ISGF3. (
  • A large number of factors influence dominance and crypticity of peptide epitopes, basically availability for MHC binding, MHC binding itself, and the recognition of the MHC:peptide complex by T cells via their antigen receptors (1). (
  • Figure 5-3-4: An MHC ClassII-peptide complex: HLA-DR1 bound with CLIP peptide. (
  • According to the data of P. M. Alyeva (1993) DR5 antigen is a risk factor of disease development, and DR4 and DRw6 antigens are resistance factors. (
  • 2000. Superantigen antagonist protects against lethal shock and defines a new domain for T-cell activation. (
  • We thank Dr. François Lemonnier for provision of HHDII-DR1 animals (which are property of the Institut Pasteur, 25-28 rue de Docteur Roux, Paris, France 75015), and Drs. George Wilding and Ajit Verma for TRAMP +/+ mice. (
  • Collectively, we described a novel syngeneic tumor model A2/DR1 mice that could be used as preclinical tool for the evaluation of antitumor immunotherapies. (
  • In contrast, studies in mice have provided proof of principle for stem cell transplantation and other therapies. (
  • Early studies with T cell-deficient nude mice were discouraging, as these mice failed to support the growth of transferred human hematopoietic cells ( 2 ). (
  • Transplantation of human hematolymphoid cells into SCID mice proved more successful, although the number of human cells that successfully engrafted in the mice was very low ( 4 ). (
  • However, lymphoid reconstitution in these mice is limited to immature B cells because residual NK activity appears to constrain development and survival of mature T and B cells ( 5 - 7 ). (
  • Using IL-10 reporter mice, scientists detected IL-10-producing Foxp3 + T cells in the kidney, blood, and secondary lymphoid tissue in a mouse model of crescentic GN. (
  • Depletion of CD4 T cells results in reactivation tuberculosis in both mice and humans ( 26 , 38 ). (
  • IFNGR1 is the ligand binding receptor and is required but not sufficient for signal transduction, whereas IFNGR2 do not bind IFNG independently but mainly plays a role in IFNG signaling and is generally the limiting factor in IFNG responsiveness. (
  • Furthermore, assembly of the immunological synapse leads to intracellular events that modulate and define the magnitude and characteristics of the T cell response. (
  • The human species, which is at a high level of evolutionary immunological accumulation, have multiple immune defense strategies which, in turn, are highly regulated. (
  • However, mesenchymal stem cell-derived EVs were shown to play a more suppressive role by shifting T cells from an activated to a T regulatory phenotype. (
  • Rheumatoid T cells have an unusual phenotype. (
  • Hyperglycemia, lipotoxic injury and insulin resistance activate a fibrotic response, not only through direct stimulation of matrix synthesis by fibroblasts, but also by promoting a fibrogenic phenotype in immune and vascular cells, and possibly also by triggering epithelial and endothelial cell conversion to a fibroblast-like phenotype. (
  • There are many studies involving autologous therapies and some allogenic therapies, based on the recovery of mobilized bone marrow cells, including mesenchymal stem cells (MSCs) and adipose derived stem cells that also include the stromal or adherent cell type that has an MSC phenotype. (
  • Recently, evidence suggests EVs to play a more dichotomic role in the regulation of the immune system, whereby an immune response may be enhanced or supressed by EVs depending on their cell of origin and its functional state. (
  • In the present review we look at recent developments in the immunobiology of RA, with focus on the role of T cells and B cells, the products they produce, including cytokines and autoantibodies, and the genetic factors potentially involved in their regulation and function. (
  • Brennan and colleagues demonstrated that the spontaneous TNFα production in RA synovium was largely T-cell dependent [ 11 ], suggesting that regulation of T-cell function might be important to control the disease. (
  • Because of the major role of CD4 T cells in the initiation and regulation of immune response, the main means of prediction based on the quantification of the specific directory in naïve CD4 T and the identification of the corresponding CD4 epitopes. (
  • Self-antigens are suppressed by regulatory T cells . (
  • On primed-naive CD4 + T cells, the expression of regulatory T cell markers was evaluated and their suppressive ability was assessed in autologous co-cultures with CD4 + effector T cells and PPD-pulsed mDCs. (
  • Dominant protection from HLA-linked autoimmunity by antigen-specific regulatory T cells. (
  • Remarkably, transfer of activin-A-induced antigen-specific regulatory T cells confers protection against allergic airway disease. (
  • INTERPRETATION: Regulatory cell therapy is achievable and safe in living-donor kidney transplant recipients, and is associated with fewer infectious complications, but similar rejection rates in the first year. (
  • Genetically modified hematopoietic stem/progenitor cells that produce IL-10-secreting regulatory T cells. (
  • Defining the structural basis by which CD4+ T cell help is invoked in an anti-tumor immune response will likely aid the design of more effective cancer immunotherapies. (
  • Finally, immunization decreased prostate tumor growth in Copenhagen rats that was associated with a Th1-type immune response. (
  • We propose that NETs are involved in the initial immune response after the injection of vaccines and plan to investigate the effect of these NETs in the activation of different antigen presenting cells and their subsequent effects on the polarisation of naïve T cells. (
  • There is compelling evidence that CD8 + cytotoxic T cells are crucial players in the protective immune response against viral infections and tumors ( 4 ). (
  • It is possible that preferential boosting of low-frequency, stalk-reactive memory B cells in response to avian influenza HAs ( 12 - 15 ) may be responsible for the low magnitude of the neutralizing antibody response. (
  • Another possible explanation is that, while healthy humans do have circulating, cross-reactive CD4 + T cells to H5 and H7 HA ( 17 - 20 ), prepandemic priming was required to generate a sufficiently robust H5-specific CD4 + T cell response and subsequent antibody response ( 20 ). (
  • Increased abundance of DR 'antigen' on the cell surface is often in response to stimulation, and, therefore, DR is also a marker for immune stimulation. (
  • To avoid transformed cells from expanding into the organism and causing pathology, effective surveillance by the adaptive immune response continuously needs to take place [ 6 - 9 ]. (
  • will be effective in inducing a protective immune response, covering the entire target population, becomes an important question. (
  • Vaccination with DNA- or peptide-based ognized by the entire target population, and vaccines relies on T cell recognition, either iii) induce an immune response of an ad- in the afferent (T cell-dependent antibody- equate isotype. (
  • In this review, we will discuss how stem cell-derived EVs may contribute toward the modulation of the immune response. (
  • The immune system is primarily designed to defend from germs and this response triggers inflammatory reactions which must be regulated in order not to generate damage to healthy tissue. (
  • Human immune-response, D-related antigen encoded by the D locus on chromosome 6 and found on lymphoid cells. (
  • Many of these secreted toxins have the properties of superantigens, nonspecifically and powerfully stimulating the host's immune response. (
  • The biological influence of hormones, immune response changes, and the role of mitochondrial defects and apoptosis also contribute to the pathogenesis of RA. (
  • ii) be recognized by the entire target population, and iii) induce an immune response of an adequate isotype. (
  • Allograft rejection is the consequence of the recipient's alloimmune response to nonself antigens expressed by donor tissues. (
  • T cells are selected in the thymus vis-à-vis self peptides but this selection is not complete so that the sequences of human origin can be recognized by CD4 T cells and trigger an immune response. (
  • response of Survivin and midkine antigens and recently cyclin B1.Our goal is to combine the CD4 and CD8 T-cell epitopes to define long fragments can be used as therapeutic vaccines against tumors. (
  • Autoimmune diseases are thought to arise from an overactive immune response of the body against substances and tissues normally present in the body. (
  • At least forty different chronic diseases are suspected or accepted as being caused by an autoimmune A condition or disease thought to arise from an overactive immune response of the body against substances and tissues normally present in the body response. (
  • This immune response protects the skin of the symptomatic host from further bacterial colonization. (
  • In the case of allogenic MSCs, delivery to an inflamed site can result in gain of immune potency with accelerated damage due to a heightened immune-mediated inflammatory response [ 5 ]. (
  • Gamma interferon (IFN-γ) produced by activated T cells is a central regulator of the immune response to M. tuberculosis ( 8 , 42 ). (
  • The B-cells of patients with recently diagnosed Type 1 (insulin-dependent) diabetes may have no response to glucose when the response to glucagon is present but attenuated. (
  • To extend the use and application of this mouse model in the field of antitumor immunotherapy, we described a tumor cell line generated from a naturally occurring tumor in A2/DR1 mouse named SARC-L1. (
  • The optimal target antigens for immunotherapy are leukemia-specific antigens. (
  • The presence of a competent immune system, whereby tumor antigens are recognized as foreign and eliminated, is fundamental to the prevention of cancer development and progression. (
  • For example, if the cell is infected by a virus, the HLA system brings fragments of the virus to the surface of the cell so that the cell can be destroyed by the immune system. (
  • The immune system uses the HLAs to differentiate self cells and non-self cells. (
  • EVs are involved in intercellular communication between multiple cell types, including those of the immune system. (
  • In 1995, a milestone study demonstrated psoriatic plaque resolution following selective apoptosis of activated T cells, without affecting KC survival or activation, thus demonstrating the crucial role of the immune system, particularly of T cells, in the disease [ 1 ]. (
  • This heterogeneity contributes to the uniqueness of each person's immune system. (
  • To circumvent pathology caused by infectious microbes and tumor growth, the host immune system must constantly clear harmful microorganisms and potentially malignant transformed cells. (
  • During this process, transformed cells become modified in such a way that they acquire increased replication fitness and resistance to the immune system [ 28 , 29 ]. (
  • Collectively, stem cell-derived EVs mainly exhibit an inhibitory effect on the immune system. (
  • Some medications, such as the classic example of D-penicillamine, may induce a disturbance of the immune system that results in the development of myasthenia gravis, whereas many other agents produce weakness by direct compromise of neuromuscular transmission. (
  • Viral reactivation from latency is quickly controlled by the immune system. (
  • With respect to the immune system of mammals, these changes have a lot to do with the interactions that occur continuously with other living species, especially microorganisms. (
  • This may be the origin of the immune system. (
  • Pretreatment activation of the immune system, as reflected by cytokines transcripts upregulation, positively correlates with treatment outcome and closely reflects liver inflammatory activity. (
  • Various pro- and anti-inflammatory factors and virus inhibiting immune system components such as cytokines and their receptors, were subject of a number of studies. (
  • The binding between potentially pathogenic peptides and MHCs is one of the most important processes in the human immune system. (
  • Are they more or less prone to develop autoimmune side effects as their system is exposed to these foreign antigens at a very early stage? (
  • Jean Dausset described the first human MHC antigen MAC (HLA-A2) as part of the Hu-1 system 5 followed by the discovery of the FOUR series 4a and 4b (HLA-Bw4 and -Bw6) by the Leiden group led by Jon van Rood in 1963 6;7 . (
  • This virus may be reactivated by the dysregulation of the host immune system or possibly by virus mutation. (
  • It has become clear that exogenous peptides alone fail to activate effective CD8+ T cell levels, and if induced, they tend to be transient in patients with a weakened or tolerized immune system. (
  • The "watchers" instead, are a very specialized population of cells belonging to the immune system known as T-Cells. (
  • Recognition of HLA incompatibilities by the immune system represents a major barrier to allogeneic hematopoietic stem cell transplantation. (
  • Thus for many patients a challenge for the histocompatibility laboratory is to identify mismatched donors or cord blood units with the lowest potential for recognition by the immune system, in particular by the direct T-cell allorecognition mode. (
  • It is a huge mistake to think the immune system as something designed to protect the human body. (
  • While autoantibodies were reported over a century ago, many scientists at the time were unwilling to accept the possibility that the immune system attacks its own cells. (
  • The study of human hematopoiesis and the development of a functional human immune system following HSC engraftment has benefited from recent advances in the SCID and other profoundly immunodeficient mouse models. (
  • Vitamin D represents a candidate protective factor for type 1 diabetes as it regulates the immune system and autoimmunity ( 2 ), and vitamin D status varies by latitude ( 3 ). (
  • exogenous antigens must compete with those derived from endogenous components. (