Sites on an antigen that interact with specific antibodies.
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.
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.
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.
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.
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.
Antigenic determinants recognized and bound by the B-cell receptor. Epitopes recognized by the B-cell receptor are located on the surface of the antigen.
Subunits of the antigenic determinant that are most easily recognized by the immune system and thus most influence the specificity of the induced antibody.
A classification of lymphocytes based on structurally or functionally different populations of cells.
Antibodies produced by a single clone of cells.
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.
The number of LYMPHOCYTES per unit volume of BLOOD.
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.
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.
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.
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.
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.
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.
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.
An encapsulated lymphatic organ through which venous blood filters.
A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.
A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.
Measure of histocompatibility at the HL-A locus. Peripheral blood lymphocytes from two individuals are mixed together in tissue culture for several days. Lymphocytes from incompatible individuals will stimulate each other to proliferate significantly (measured by tritiated thymidine uptake) whereas those from compatible individuals will not. In the one-way MLC test, the lymphocytes from one of the individuals are inactivated (usually by treatment with MITOMYCIN or radiation) thereby allowing only the untreated remaining population of cells to proliferate in response to foreign histocompatibility antigens.
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).
Mucoproteins isolated from the kidney bean (Phaseolus vulgaris); some of them are mitogenic to lymphocytes, others agglutinate all or certain types of erythrocytes or lymphocytes. They are used mainly in the study of immune mechanisms and in cell culture.
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.
Lymphocytes that show specificity for autologous tumor cells. Ex vivo isolation and culturing of TIL with interleukin-2, followed by reinfusion into the patient, is one form of adoptive immunotherapy of cancer.
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)
A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*02 allele family.
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.
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.
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.
Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.
Established cell cultures that have the potential to propagate indefinitely.
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.
A MANNOSE/GLUCOSE binding lectin isolated from the jack bean (Canavalia ensiformis). It is a potent mitogen used to stimulate cell proliferation in lymphocytes, primarily T-lymphocyte, cultures.
The demonstration of the cytotoxic effect on a target cell of a lymphocyte, a mediator released by a sensitized lymphocyte, an antibody, or complement.
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.
The number of WHITE BLOOD CELLS per unit volume in venous BLOOD. A differential leukocyte count measures the relative numbers of the different types of white cells.
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)
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.
Substances elaborated by viruses that have antigenic activity.
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.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
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 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.
The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.
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.
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.
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.
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.
They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.
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.
The transfer of lymphocytes from a donor to a recipient or reinfusion to the donor.
Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation.
T-cell enhancement of the B-cell response to thymic-dependent antigens.
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.
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.
Substances that stimulate mitosis and lymphocyte transformation. They include not only substances associated with LECTINS, but also substances from streptococci (associated with streptolysin S) and from strains of alpha-toxin-producing staphylococci. (Stedman, 25th ed)
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.
The major group of transplantation antigens in the mouse.
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.
Glycoproteins found on the membrane or surface of cells.
The in vitro formation of clusters consisting of a cell (usually a lymphocyte) surrounded by antigenic cells or antigen-bearing particles (usually erythrocytes, which may or may not be coated with antibody or antibody and complement). The rosette-forming cell may be an antibody-forming cell, a memory cell, a T-cell, a cell bearing surface cytophilic antibodies, or a monocyte possessing Fc receptors. Rosette formation can be used to identify specific populations of these cells.
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.
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).
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
Substances that are recognized by the immune system and induce an immune reaction.
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).
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.
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.
An integrin heterodimer widely expressed on cells of hematopoietic origin. CD11A ANTIGEN comprises the alpha chain and the CD18 antigen (ANTIGENS, CD18) the beta chain. Lymphocyte function-associated antigen-1 is a major receptor of T-CELLS; B-CELLS; and GRANULOCYTES. It mediates the leukocyte adhesion reactions underlying cytolytic conjugate formation, helper T-cell interactions, and antibody-dependent killing by NATURAL KILLER CELLS and granulocytes. Intracellular adhesion molecule-1 has been defined as a ligand for lymphocyte function-associated antigen-1.
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 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.
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
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.
The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.
Cell surface glycoproteins on lymphocytes and other leukocytes that mediate adhesion to specialized blood vessels called high endothelial venules. Several different classes of lymphocyte homing receptors have been identified, and they appear to target different surface molecules (addressins) on high endothelial venules in different tissues. The adhesion plays a crucial role in the trafficking of lymphocytes.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
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.
Proteins prepared by recombinant DNA technology.
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.
Local surface sites on antibodies which react with antigen determinant sites on antigens (EPITOPES.) They are formed from parts of the variable regions of FAB FRAGMENTS.
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.
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.
Proteins that share the common characteristic of binding to carbohydrates. Some ANTIBODIES and carbohydrate-metabolizing proteins (ENZYMES) also bind to carbohydrates, however they are not considered lectins. PLANT LECTINS are carbohydrate-binding proteins that have been primarily identified by their hemagglutinating activity (HEMAGGLUTININS). However, a variety of lectins occur in animal species where they serve diverse array of functions through specific carbohydrate recognition.
Receptors present on activated T-LYMPHOCYTES and B-LYMPHOCYTES that are specific for INTERLEUKIN-2 and play an important role in LYMPHOCYTE ACTIVATION. They are heterotrimeric proteins consisting of the INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT, the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT, and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN.
Immunoglobulins produced in response to VIRAL ANTIGENS.
Ratio of T-LYMPHOCYTES that express the CD4 ANTIGEN to those that express the CD8 ANTIGEN. This value is commonly assessed in the diagnosis and staging of diseases affecting the IMMUNE SYSTEM including HIV INFECTIONS.
Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.
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).
Substances elaborated by bacteria that have antigenic activity.
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.
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.
The measurement of infection-blocking titer of ANTISERA by testing a series of dilutions for a given virus-antiserum interaction end-point, which is generally the dilution at which tissue cultures inoculated with the serum-virus mixtures demonstrate cytopathology (CPE) or the dilution at which 50% of test animals injected with serum-virus mixtures show infectivity (ID50) or die (LD50).
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.)
Form of adoptive transfer where cells with antitumor activity are transferred to the tumor-bearing host in order to mediate tumor regression. The lymphoid cells commonly used are lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL). This is usually considered a form of passive immunotherapy. (From DeVita, et al., Cancer, 1993, pp.305-7, 314)
A calcium-dependent pore-forming protein synthesized in cytolytic LYMPHOCYTES and sequestered in secretory granules. Upon immunological reaction between a cytolytic lymphocyte and a target cell, perforin is released at the plasma membrane and polymerizes into transmembrane tubules (forming pores) which lead to death of a target cell.
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.
The number of CD4-POSITIVE T-LYMPHOCYTES per unit volume of BLOOD. Determination requires the use of a fluorescence-activated flow cytometer.
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.
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.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
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.
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).
Elements of limited time intervals, contributing to particular results or situations.
Specialized tissues that are components of the lymphatic system. They provide fixed locations within the body where a variety of LYMPHOCYTES can form, mature and multiply. The lymphoid tissues are connected by a network of LYMPHATIC VESSELS.
Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.
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.
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.
Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).
A class of lymphocytes characterized by the lack of surface markers specific for either T or B lymphocytes.
A method for the detection of very small quantities of antibody in which the antigen-antibody-complement complex adheres to indicator cells, usually primate erythrocytes or nonprimate blood platelets. The reaction is dependent on the number of bound C3 molecules on the C3b receptor sites of the indicator cell.
A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.
Proteins secreted from an organism which form membrane-spanning pores in target cells to destroy them. This is in contrast to PORINS and MEMBRANE TRANSPORT PROTEINS that function within the synthesizing organism and COMPLEMENT immune proteins. These pore forming cytotoxic proteins are a form of primitive cellular defense which are also found in human LYMPHOCYTES.
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.
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.
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.
A soluble factor produced by activated T-LYMPHOCYTES that induces the expression of MHC CLASS II GENES and FC RECEPTORS on B-LYMPHOCYTES and causes their proliferation and differentiation. It also acts on T-lymphocytes, MAST CELLS, and several other hematopoietic lineage 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.
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.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
The processes triggered by interactions of ANTIBODIES with their ANTIGENS.
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.
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.
Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection.
Adherence of cells to surfaces or to other cells.
A family of serine endopeptidases found in the SECRETORY GRANULES of LEUKOCYTES such as CYTOTOXIC T-LYMPHOCYTES and NATURAL KILLER CELLS. When secreted into the intercellular space granzymes act to eliminate transformed and virus-infected host cells.
Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
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.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Small synthetic peptides that mimic surface antigens of pathogens and are immunogenic, or vaccines manufactured with the aid of recombinant DNA techniques. The latter vaccines may also be whole viruses whose nucleic acids have been modified.
A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
Leukemia associated with HYPERPLASIA of the lymphoid tissues and increased numbers of circulating malignant LYMPHOCYTES and lymphoblasts.
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.
The type species of LYMPHOCRYPTOVIRUS, subfamily GAMMAHERPESVIRINAE, infecting B-cells in humans. It is thought to be the causative agent of INFECTIOUS MONONUCLEOSIS and is strongly associated with oral hairy leukoplakia (LEUKOPLAKIA, HAIRY;), BURKITT LYMPHOMA; and other malignancies.
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 transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.
A round-to-oval mass of lymphoid tissue embedded in the lateral wall of the PHARYNX. There is one on each side of the oropharynx in the fauces between the anterior and posterior pillars of the SOFT PALATE.
Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.
Antigens associated with specific proteins of the human adult T-cell immunodeficiency virus (HIV); also called HTLV-III-associated and lymphadenopathy-associated virus (LAV) antigens.
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 malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)
Vaccines or candidate vaccines designed to prevent or treat cancer. Vaccines are produced using the patient's own whole tumor cells as the source of antigens, or using tumor-specific antigens, often recombinantly produced.
Recombinant DNA vectors encoding antigens administered for the prevention or treatment of disease. The host cells take up the DNA, express the antigen, and present it to the immune system in a manner similar to that which would occur during natural infection. This induces humoral and cellular immune responses against the encoded antigens. The vector is called naked DNA because there is no need for complex formulations or delivery agents; the plasmid is injected in saline or other buffers.
Transfer of immunity from immunized to non-immune host by administration of serum antibodies, or transplantation of lymphocytes (ADOPTIVE TRANSFER).
The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction.
Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (IMMUNOTHERAPY, ADOPTIVE).
Proteins isolated from the roots of the pokeweed, Phytolacca americana, that agglutinate some erythrocytes, stimulate mitosis and antibody synthesis in lymphocytes, and induce activation of plasma cells.
An increased reactivity to specific antigens mediated not by antibodies but by cells.
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 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.
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.
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.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Layers of protein which surround the capsid in animal viruses with tubular nucleocapsids. The envelope consists of an inner layer of lipids and virus specified proteins also called membrane or matrix proteins. The outer layer consists of one or more types of morphological subunits called peplomers which project from the viral envelope; this layer always consists of glycoproteins.
A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.
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.
Suspensions of attenuated or killed viruses administered for the prevention or treatment of infectious viral disease.
A species of the genus MACACA inhabiting India, China, and other parts of Asia. The species is used extensively in biomedical research and adapts very well to living with humans.
DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.
A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*03 allele family.
White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).
Reduction in the number of lymphocytes.
The rate dynamics in chemical or physical systems.
The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.
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.
The type species of ORTHOPOXVIRUS, related to COWPOX VIRUS, but whose true origin is unknown. It has been used as a live vaccine against SMALLPOX. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of VACCINIA VIRUS.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Species of the genus LENTIVIRUS, subgenus primate immunodeficiency viruses (IMMUNODEFICIENCY VIRUSES, PRIMATE), that induces acquired immunodeficiency syndrome in monkeys and apes (SAIDS). The genetic organization of SIV is virtually identical to HIV.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
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.
Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs.
Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.
The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.
Vaccines or candidate vaccines containing inactivated HIV or some of its component antigens and designed to prevent or treat AIDS. Some vaccines containing antigens are recombinantly produced.
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.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP.
Antibodies that reduce or abolish some biological activity of a soluble antigen or infectious agent, usually a virus.
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.
Proteins coded by the retroviral gag gene. The products are usually synthesized as protein precursors or POLYPROTEINS, which are then cleaved by viral proteases to yield the final products. Many of the final products are associated with the nucleoprotein core of the virion. gag is short for group-specific antigen.
Cell adhesion molecule and CD antigen that serves as a homing receptor for lymphocytes to lymph node high endothelial venules.
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.
A protein extracted from boiled culture of tubercle bacilli (MYCOBACTERIUM TUBERCULOSIS). It is used in the tuberculin skin test (TUBERCULIN TEST) for the diagnosis of tuberculosis infection in asymptomatic persons.
The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.
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.

Crystal structure of an MHC class I presented glycopeptide that generates carbohydrate-specific CTL. (1/4245)

T cell receptor (TCR) recognition of nonpeptidic and modified peptide antigens has been recently uncovered but is still poorly understood. Immunization with an H-2Kb-restricted glycopeptide RGY8-6H-Gal2 generates a population of cytotoxic T cells that express both alpha/beta TCR, specific for glycopeptide, and gamma/delta TCR, specific for the disaccharide, even on glycolipids. The crystal structure of Kb/RGY8-6H-Gal2 now demonstrates that the peptide and H-2Kb structures are unaffected by the peptide glycosylation, but the central region of the putative TCR binding site is dominated by the extensive exposure of the tethered carbohydrate. These features of the Kb/RGY8-6H-Gal2 structure are consistent with the individual ligand binding preferences identified for the alpha/beta and gamma/delta TCRs and thus explain the generation of a carbohydrate-specific T cell response.  (+info)

Crystal structures of two H-2Db/glycopeptide complexes suggest a molecular basis for CTL cross-reactivity. (2/4245)

Two synthetic O-GlcNAc-bearing peptides that elicit H-2Db-restricted glycopeptide-specific cytotoxic T cells (CTL) have been shown to display nonreciprocal patterns of cross-reactivity. Here, we present the crystal structures of the H-2Db glycopeptide complexes to 2.85 A resolution or better. In both cases, the glycan is solvent exposed and available for direct recognition by the T cell receptor (TCR). We have modeled the complex formed between the MHC-glycopeptide complexes and their respective TCRs, showing that a single saccharide residue can be accommodated in the standard TCR-MHC geometry. The models also reveal a possible molecular basis for the observed cross-reactivity patterns of the CTL clones, which appear to be influenced by the length of the CDR3 loop and the nature of the immunizing ligand.  (+info)

Phenotypic and functional characterization of CD8(+) T cell clones specific for a mouse cytomegalovirus epitope. (3/4245)

A series of CD8(+) T cell clones, specific for the IE1 epitope YPHFMPTNL, of the immediate-early protein 1 of the murine cytomegalovirus (MCMV) were generated in order to determine their protective activity against this infection and correlate their phenotypic markers with antiviral activity. We found that the adoptive transfer of three of these anti-MCMV CD8(+) T cell clones into irradiated naive mice resulted in protection against challenge, while another CD8(+) T cell clone, of the same specificity, failed to confer protection. The clones that conferred protection against lethal challenge reduced greatly viral replication in the lung and other organs of the mice. Using one of the protective anti-MCMV CD8(+) T cell clones we found that in order to be fully protective the cells had to be transferred to recipient mice no later than 1 day after MCMV challenge. The adoptive transfer of these CD8(+) T cell clones also protected CD4(+) T-cell-depleted mice. Phenotypic characterization of the anti-MCMV clones revealed that the nonprotective clone expressed very low levels of CD8 molecules and produced only small amounts of TNF-alpha upon antigenic stimulation. Most importantly, our current study demonstrates that this MHC class I-restricted IE1 epitope of MCMV is efficiently presented to CD8(+) T cell clones in vivo and further strengthens the possibility of the potential use of CD8(+) T cell clones as immunotherapeutic tools against cytomegalovirus-induced disease.  (+info)

Immune response to the immunodominant epitope of mouse hepatitis virus is polyclonal, but functionally monospecific in C57Bl/6 mice. (4/4245)

Mutations in an immunodominant CD8 CTL epitope (S-510-518) are selected in mice persistently infected with the neurotropic JHM strain of mouse hepatitis virus. These mutations abrogate recognition by T cells harvested from the infected CNS in direct ex vivo cytotoxicity assays. Previous reports have suggested that, in general, an oligoclonal, monospecific T cell response contributes to the selection of CTL escape mutants. Herein, we show that, in MHV-JHM-infected mice, the CD8 T cell response after intraperitoneal infection is polyclonal and diverse. This diverse response was shown to include both polyclonal and oligoclonal components. The polyclonal data were shown to fit a logarithmic distribution. With regard to specificity, we used a panel of peptide analogues of epitope S-510-518 and spleen-derived CD8 T cell lines to determine why only a subset of possible mutations was selected in persistently infected mice. At a given position in the epitope, the mutations identified in in vivo isolates were among those that resulted in the greatest loss of recognition. However, not all such mutations were selected, suggesting that additional factors must contribute to selection in vivo. By extrapolation of these results to the persistently infected CNS, they suggest that the selection of CTL escape mutants requires the presence of a monospecific T cell response but also show that this response need not be oligoclonal.  (+info)

Induction of CD8+ T cell-mediated protective immunity against Trypanosoma cruzi. (5/4245)

Trypanosoma cruzi was transformed with the Plasmodium yoelii gene encoding the circum-sporozoite (CS) protein, which contains the well-characterized CD8+ T cell epitope, SYVPSAEQI. In vivo and in vitro assays indicated that cells infected with the transformed T. cruzi could process and present this malaria parasite-derived class I MHC-restricted epitope. Immunization of mice with recombinant influenza and vaccinia viruses expressing the SYVPSAEQI epitope induced a large number of specific CD8+ T cells that strongly suppressed parasitemia and conferred complete protection against the acute T. cruzi lethal infection. CD8+ T cells mediated this immunity as indicated by the unrelenting parasitemia and high mortality observed in immunized mice treated with anti-CD8 antibody. This study demonstrated, for the first time, that vaccination of mice with vectors designed to induce CD8+ T cells is effective against T. cruzi infection.  (+info)

In vivo and in vitro activation of T cells after administration of Ag-negative heat shock proteins. (6/4245)

Heat shock proteins (HSP) Hsp70 and gp96 prime class I-restricted cytotoxic T cells against Ags present in the cells from which they were isolated. The immunization capacity of HSPs is believed to rely on their ability to bind antigenic peptides. In this study, we employed the well-established OVA and beta-galactosidase (beta-gal) antigenic model systems. We show that in vitro long-term established OVA and beta-gal-specific CTL clones release TNF-alpha and IFN-gamma when incubated with Ag-negative Hsp70 and gp96. In the absence of antigenic peptides, HSP-mediated secretion of TNF-alpha and IFN-gamma requires cell contact of the APC with the T cell but is not MHC-I restricted. Moreover, Hsp70 molecules purified from Ag-negative tissue, e.g., negative for antigenic peptide, are able to activate T cells in vivo, leading to significant higher frequencies in OVA-specific CD8+ T cells. In unprimed animals, these T cells lyse OVA-transfected cell lines and produce TNF-alpha and IFN-gamma after Ag stimulus. Taken together our data show that, besides the well-established HSP/peptide-specific CTL induction and activation, a second mechanism exists by which Hsp70 and gp96 molecules activate T cells in vivo and in vitro.  (+info)

Fas-mediated suicide of tumor-reactive T cells following activation by specific tumor: selective rescue by caspase inhibition. (7/4245)

CD8+ T lymphocytes that specifically recognize tumor cells can be isolated and expanded ex vivo. While the lytic properties of these cells have been well described, their fate upon encounter with cognate tumor is not known. We performed reverse 51Cr release assays in which the lymphocyte effectors rather than the tumor cell targets were radioactively labeled. We found that melanoma tumor cells caused the apoptotic death of tumor-specific T cells only upon specific MHC class I-restricted recognition. This death was entirely blockable by the addition of an Ab directed against the Fas death receptor (APO-1, CD95). Contrary to the prevailing view that tumor cells cause the death of anti-tumor T cells by expressing Fas ligand (FasL), our data suggested that FasL was instead expressed by T lymphocytes upon activation. While the tumor cells did not express FasL by any measure (including RT-PCR), functional FasL (as well as FasL mRNA) was consistently found on activated anti-tumor T cells. We could successfully block the activation-induced cell death with z-VAD-fmk, a tripeptide inhibitor of IL-1 beta-converting enzyme homologues, or with anti-Fas mAbs. Most importantly, these interventions did not inhibit T cell recognition as measured by IFN-gamma release, nor did they adversely affect the specific lysis of tumor cell targets. These results imply that Fas-mediated activation-induced cell death could be a limiting factor in the in vivo efficacy of adoptive transfer of class I-restricted CD8+ T cells and provide a means of potentially enhancing their growth in vitro as well as their function in vivo.  (+info)

Enumeration of antigen-presenting cells in mice infected with Sendai virus. (8/4245)

Substantial progress has been made in understanding Ag presentation to T cells; however, relatively little is known about the location and frequency of cells presenting viral Ags during a viral infection. Here, we took advantage of a highly sensitive system using lacZ-inducible T cell hybridomas to enumerate APCs during the course of respiratory Sendai virus infection in mice. Using lacZ-inducible T cell hybridomas specific for the immunodominant hemagglutinin-neuraminidase HN421-436/I-Ab and nucleoprotein NP324-332/Kb epitopes, we detected APCs in draining mediastinal lymph nodes (MLNs), in cervical lymph nodes, and also in the spleen. HN421-436/I-Ab- and NP324-332/Kb-presenting cells were readily detectable between days 3 and 9 postinfection, with more APCs present in the MLN than in the cervical lymph nodes. Interestingly, no infectious virus was detected in lymphoid tissue beyond day 6, suggesting that a depot of noninfectious viral Ag survives, in some form, for 2-3 days after viral clearance. Fractionation of the MLN demonstrated that APC frequency was enriched in dendritic cells and macrophages but depleted in the B cell population, suggesting that B cells do not form a large population of APCs during the primary response to this virus.  (+info)

HIV-epitope-specific T cell responses are critical components of the natural immune response to HIV infection, but these cells often become dysfunctional in chronic infection. Structural diversity within the epitope-specific T cell receptor (TCR) repertoire is likely beneficial in the suppression of viral epitope variants. However, the relationship between the structural and clonotypic composition of the HIV-specific TCR repertoire, clonotypic surface and functional phenotype, and avidity for and exposure to antigen is poorly defined. Dominant and sub-dominant epitope-specific T cell clonotypes were identified and the TCR repertoire was assessed over time. Surface expression of PD-1, CD38, CD127, CD45RO, and CCR7 was measured and used to define exhaustion and memory profiles on epitope-specific T cell populations during chronic infection and after initiation of antiretroviral therapy. Dominant clonotypes in chronic infection express a surface phenotype consistent with exhaustion which is ...
BACKGROUNDː The most cause of cancer-related death in women population is breast cancer (BC). Hence, efforts to develop an effective treatment against BC are needed. Since the large proportion of BC is due to over-expression of tumor-associated antigens (TAAs), multi-epitope cancer vaccines are considered as a promising therapeutic approach. The aim of the current study is the production of the novel multi-epitope peptide vaccine against BC in a prokaryotic host. Our novel multi-epitope BC vaccine consists of four sections: 1) cytotoxic T lymphocytes epitopes from human epidermal growth factor receptor, heparanase, mucin 1 protein; 2) helper T lymphocytes epitopes from survivin; 3) a segment of Por B protein a immunostimulatory adjuvant, which was selected from Neisseria meningitides by bioinformatics analysis; 4) a segment of murine ULBP-like transcript 1, which binds to a natural killer group 2 member D receptor in tumor microenvironment with high affinity and stimulates innate immune ...
CD8+ T cells have the potential to control HSV-2 infection. However, limited information has been available on CD8+ T cell epitopes or the functionality of antigen specific T cells during infection or following immunization with experimental vaccines. Peptide panels from HSV-2 proteins ICP27, VP22 and VP13/14 were selected from in silico predictions of binding to human HLA-A*0201 and mouse H-2Kd, Ld and Dd molecules. Nine previously uncharacterized CD8+ T cell epitopes were identified from HSV-2 infected BALB/c mice. HSV-2 specific peptide sequences stabilized HLA-A*02 surface expression with intermediate or high affinity binding. Peptide specific CD8+ human T cell lines from peripheral blood lymphocytes were generated from a HLA-A*02+ donor. High frequencies of peptide specific CD8+ T cell responses were elicited in mice by DNA vaccination with ICP27, VP22 and VP13/14, as demonstrated by CD107a mobilization. Vaccine driven T cell responses displayed a more focused immune response than those induced
Free resource for searching and exporting immune epitopes. Includes more than 95% of all published infectious disease, allergy, autoimmune, and transplant epitope data.
Advances in the field of T cell immunology have contributed to the understanding that cross-reactivity is an intrinsic characteristic of the T cell receptor (TCR), and that each TCR can potentially interact with many different T cell epitopes. To better define the potential for TCR cross-reactivity between epitopes derived from the human genome, the human microbiome, and human pathogens, we developed a new immunoinformatics tool, JanusMatrix, that represents an extension of the validated T cell epitope mapping tool, EpiMatrix. Initial explorations, summarized in this synopsis, have uncovered what appear to be important differences in the TCR cross-reactivity of selected regulatory and effector T cell epitopes with other epitopes in the human genome, human microbiome, and selected human pathogens. In addition to exploring the T cell epitope relationships between human self, commensal and pathogen, JanusMatrix may also be useful to explore some aspects of heterologous immunity and to examine T cell
Jørgensen KW, Rasmussen M, Buus S, Nielsen M. NetMHCstab - predicting stability of peptide:MHC-I complexes; impacts for CTL epitope...
Jørgensen KW, Rasmussen M, Buus S, Nielsen M. NetMHCstab - predicting stability of peptide:MHC-I complexes; impacts for CTL epitope...
The specificity of T cells is determined by the TCR. T cell populations activated and expanded during most in vivo antigen challenges are highly complex, with diverse TCR repertoires, complicating the detection of these cells. The ideal reagent to identify complex epitope-specific T cell populations would be the natural ligand of the TCR, the MHC/epitope complex. However, the affinity of the TCR-MHC/epitope interaction is very low; the association is characterized by a particularly high dissociation rate. To increase the overall avidity of this interaction, MHC/epitope complexes are multimerized into e.g. tetramers. MHC tetramer reagents conjugated with a fluorescent dye can be used in flow cytometry, allowing highly specific detection and isolation of (complex) epitope specific T cell populations directly ex vivo.. The generation of MHC class I multimer reagents has become well established over the past few years. Beta-2-microglobulin and the heavy chains (HC) of MHC molecules are expressed as ...
TCR affinity associated with functional differences between dominant and subdominant SIV epitope-specific CD8+ T cells in Mamu-A*01+ rhesus monkeys.
Free resource for searching and exporting immune epitopes. Includes more than 95% of all published infectious disease, allergy, autoimmune, and transplant epitope data.
Strategy for Identifying Dendritic Cell-Processed CD4 T Cell Epitopes from the HIV Gag p24 Protein. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
ECIA™ Intracellular cytokine staining assay is utilized to detect the antigen-specific T cell responses, immunogenic analysis, epitope discovery at a single cell level for both clinical studies and scientific researches.
We have recently described the first true genome-wide screen for CD4+ T cell reactivity directed against MTB in latent TB infected individuals. The approach relied on predictions of HLA binding capacity for a panel of DR, DP and DQ alleles representative of those most commonly expressed in the general population, coupled with high throughput ELISPOT assays. The results identified hundreds of novel epitopes and antigens, and documented the novel observation that T cells in latent MTB infection are confined to the CXCR3+CCR6+ phenotype and largely directed against three antigenic
EpiToolKit provides a collection of methods from computational immunology for the development of novel epitope-based vaccines including HLA ligand or potential T-Cell epitope prediction, an epitope selection framework for vaccine design, and a method to design optimal string-of-beads vaccines. Additionally, EpiToolKit provides several other tools ranging from HLA typing based on NGS data, to prediction of polymorphic peptides ...
MHC Tetramers for detecting specific T-cell populations. Easy immuophenotyping of your t-cell sample! Class I and II antigen specific tetramers available.
Multiple lines of evidence support a role for CD8(+) T cells in control of acute/early HIV replication; however, features of the primary HIV-specific CD8(+) T cell response that may impact on the efficiency of containment of early viral replication remain poorly defined. In this study, we performed a novel, comprehensive analysis of the kinetics of expansion of components of the HIV-specific CD8(+) T cell response in 21 acutely infected individuals. Epitope-specific T cell responses expanded asynchronously during primary infection in all subjects. The most rapidly expanded responses peaked as early as 5 days following symptomatic presentation and were typically of very limited epitope breadth. Responses of additional specificities expanded and contracted in subsequent waves, resulting in successive shifts in the epitope immunodominance hierarchy over time. Sequence variation and escape were temporally associated with the decline in magnitude of only a subset of T cell responses, suggesting that other
Cytotoxic T lymphocytes (CTLs) play a key role in the control of persistent viral infections. Differences in the quality of this cellular immune response influence the long-term outcome of such infections, but the factors that determine which virus-derived peptide epitopes are targeted by CTLs remain poorly understood. Here, we examine the antigen-processing requirements of three human leukocyte antigen (HLA) A*0201-restricted HIV-1 CTL epitopes. Each of these three peptides appears to be generated by a distinct proteolytic pathway, despite presentation on the cell surface in association with the same HLA class I molecule. Presentation of the commonly immunodominant SLYNTVATL (HIV-1 p17 Gag; residues 77-85) epitope was unaffected by inhibition of the proteasome with lactacystin, but was dependent on the presence of the beta-subunit LMP7. These findings are consistent with emerging data on the complexity of peptide epitope generation, and suggest that differences in antigen processing might contribute to
The chimeric antibodies anti-CD20 rituximab (Rtx) and anti-TNFa infliximab (Ifx) induce antidrug antibodies (ADAs) in many patients with inflammatory diseases. Because of the key role of CD4 T lymphocytes in the initiation of antibody responses, we localized the CD4 T cell epitopes of Rtx and Ifx. With the perspective to anticipate immunogenicity of therapeutic antibodies, identification of the CD4 T cell epitopes was performed using cells collected in healthy donors. Nine T cell epitopes were identified in the variable chains of both antibodies by deriving CD4 T cell lines raised against either Rtx or Ifx. The T cell epitopes often exhibited a good affinity for human leukocyte antigen (HLA)-DR molecules and were part of the peptides identified by MHC-associated peptide proteomics assay from HLA-DR molecules of dendritic cells (DCs) loaded with the antibodies. Two-third of the T cell epitopes identified from the healthy donors stimulated peripheral blood mononuclear cells from patients having ...
The ability of HIV-1-specific CD8(+) T cell responses to recognize epitope variants resulting from viral sequence variation in vivo may affect the ease with which HIV-1 can escape T cell control and impact on the rate of disease progression in HIV-1-infected humans. Here, we studied the functional cross-reactivity of CD8 responses to HIV-1 epitopes restricted by HLA class I alleles associated with differential prognosis of infection. We show that the epitope-specific responses exhibiting the most efficient cross-recognition of amino acid-substituted variants were those strongly associated with delayed progression to disease. Not all epitopes restricted by the same HLA class I allele showed similar variant cross-recognition efficiency, consistent with the hypothesis that the reported associations between particular HLA class I alleles and rate of disease progression may be due to the quality of responses to certain critical epitopes. Irrespective of their efficiency of functional cross-recognition, CD8
The present study focused on three Gag CTL epitopes restricted by three common HLA alleles in Japanese people (24). The Gag protein is most commonly targeted by CTL-inducing HIV/AIDS vaccines (15). In our endogenous expression system, three A*0201-restricted epitope variants and one B*5101-restricted epitope variant escaped from the wild-type CTL recognition, and four A24-restricted epitope variants escaped from the A24-restricted 3R mutant-reactive CTL recognition. Intriguingly, two A*0201-restricted variants and three A24-restricted variants escaped from CTL killing when the gag clones were expressed endogenously in the target cells by the HIV-1 vector, despite the fact that the synthetic variant peptides were well recognized by the CTLs when loaded onto the MHC class I molecule exogenously. The peptide titration experiments have revealed that the strength of these variant peptides recognition was almost equivalent to that of the A*0201-restricted wild-type peptide or the A24-restricted 3R ...
The interaction between a CD4+ TH cell and an antigen presenting cell (APC) is a finely tuned event in adaptive immunity. The affinity is dictated by the T cell receptor (TCR) and the characteristics of antigenic peptide epitopes presented on the major histocompatibility complex class II (pMHC class II) molecules on APCs. Due to the high degree of polymorphism in MHC molecules and the vast repertoire of epitopes that may be presented on each, it is an immense challenge to predict epitopes relevant to disease and homeostasis. It would therefore be of very high value to develop a technology that allows for precise experimental identification of T cell epitopes in the absence of any prior knowledge of the relevant antigen, as long as one has access to T cells. We have developed a novel and generic combinatorial display system for MHC class II, based on phage display. Using phage display, one can probe an epitope sequence space orders of magnitude larger than any cellular or chemical system. As a ...
TY - JOUR. T1 - Refinement in the production and purification of recombinant HCMV IE1-pp65 protein for the generation of epitope-specific T cell immunity. AU - Nguyen, Thi Hoang Oanh. AU - Mifsud, Nicole Andrea. AU - Stewart, Lisbeth A. AU - Rose, Mingus J. AU - Etto, Tamara L. AU - Williamson, Nicholas A. AU - Purcell, Anthony Wayne. AU - Kotsimbos, Tom C. AU - Schwarer, Anthony. PY - 2008. Y1 - 2008. UR - M3 - Article. VL - 61. SP - 22. EP - 30. JO - Protein Expression and Purification. JF - Protein Expression and Purification. SN - 1046-5928. IS - 1. ER - ...
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Treatment of invasive adenovirus (Ad) disease in hematopoietic stem cell transplant (SCT) recipients with capsid protein hexon-specific donor T cells is under investigation. We propose that cytotoxic T cells (CTLs) targeted to the late protein hexon may be inefficient in vivo because the early Ad protein E3-19K downregulates HLA class I antigens in infected cells. In this study, CD8+ T cells targeted to highly conserved HLA A2-restricted epitopes from the early regulatory protein DNA polymerase (P-977) and late protein hexon (H-892) were compared in peripheral blood (PB) and tonsils of naturally infected adults. In tonsils, epitope-specific pentamers detected a significantly higher frequency of P-977+CD8+ T cells compared to H-892+CD8+ T cells; this trend was reversed in PB. Tonsil epitope-specific CD8+ T cells expressed IFN-γ and IL-2 but not perforin or TNF-α, whereas PB T cells were positive for IFN-γ, TNF-α, and perforin. Tonsil epitope-specific T cells expressed lymphoid homing marker CCR7 and
Immune monitoring of T cell responses increasingly relies on the use of peptide pools. Peptides, when restricted by the same HLA allele, and presented from within the same peptide pool, can compete for HLA binding sites. What impact such competition has on functional T cell stimulation, however, is not clear. Using a model peptide pool that is comprised of 32 well-defined viral epitopes from Cytomegalovirus, Epstein-Barr virus, and Influenza viruses (CEF peptide pool), we assessed peptide competition in PBMC from 42 human subjects. The magnitude of the peptide pool-elicited CD8 T cell responses was a mean 79% and a median 77% of the sum of the CD8 T cell responses elicited by the individual peptides. Therefore, while the effect of peptide competition was evident, it was of a relatively minor magnitude. By studying the dose-response curves for individual CEF peptides, we show that several of these peptides are present in the CEF-pool at concentrations that are orders of magnitude in excess of what is
Despite progress toward understanding the correlates of protective T cell immunity in HIV infection, the optimal approach to Ag delivery by vaccination remains uncertain. We characterized two immunodominant CD8 T cell populations generated in response to immunization of BALB/c mice with a replication-deficient adenovirus serotype 5 vector expressing the HIV-derived Gag and Pol proteins at equivalent levels. The Gag-AI9/H-2Kd epitope elicited high-avidity CD8 T cell populations with architecturally diverse clonotypic repertoires that displayed potent lytic activity in vivo. In contrast, the Pol-LI9/H-2Dd epitope elicited motif-constrained CD8 T cell repertoires that displayed lower levels of physical avidity and lytic activity despite equivalent measures of overall clonality. Although low-dose vaccination enhanced the functional profiles of both epitope-specific CD8 T cell populations, greater polyfunctionality was apparent within the Pol-LI9/H-2Dd specificity. Higher proportions of central ...
Fingerprint Dive into the research topics of Recognition of naturally processed and ovarian cancer reactive CD8 ,sup,+,/sup, T cell epitopes within a promiscuous HLA class II T-helper region of NY-ESO-1. Together they form a unique fingerprint. ...
easYmer HLA-B*46:01 MHC Tetramers Kit can be used to generate monomers with your choice of peptide and to analyze T-cells by flow cytometry.
A method for updating detecting and loading CD volume indexes from a multiple-CD set to a cumulative volume table contained in a computer memory. The method employs an volume index file on each intermediate CD of the set along with a dual index file feature on the last CD of the set. The second index file on the last CD is a cumulative file of all the index files contained on all the CDs of the set. The cumulative index file on the last CD is compared to the cumulative volume table to generate a list of missing volumes which have not already been loaded into computer memory. The method permits determining whether a given CD is a single CD or a CD that is one of a multiple-CD set by detecting the presence of a second volume index file on the CD.
p286/I-Ag7 tetramer-positive CD4+ T cells from G286 mice delay diabetes transfer. Tetramer-positive and -negative cells were sorted from G286 lymph node cells w
Moradian N, Ochs HD, Sedikies C, Hamblin MR, Camargo CA Jr, Martinez JA, Biamonte JD, Abdollahi M, Torres PJ, Nieto JJ, Ogino S, Seymour JF, Abraham A, Cauda V, Gupta S, Ramakrishna S, Sellke FW, Sorooshian A, Wallace Hayes A, Martinez-Urbistondo M, Gupta M, Azadbakht L, Esmaillzadeh A, Kelishadi R, Esteghamati A, Emam-Djomeh Z, Majdzadeh R, Palit P, Badali H, Rao I, Saboury AA, Jagan Mohan Rao L, Ahmadieh H, Montazeri A, Fadini GP, Pauly D, Thomas S, Moosavi-Movahed AA, Aghamohammadi A, Behmanesh M, Rahimi-Movaghar V, Ghavami S, Mehran R, Uddin LQ, Von Herrath M, Mobasher B, Rezaei N. ...
Dear Netters, Does anyone know of any software for the prediction of T-cell epitopes from peptide sequences? I have access to Mac, PC, VAX, SG & UNIX so the program format does not matter. Hope to hear from someone soon! Thanks, Brian Robertson Max-Planck-Institut fuer Biologie Abt. Infektionsbiologie D74 Tuebingen, FRG. Email robertson at ...
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CTL recognition and antagonism by naturally occurring p17 variants. Recognition of variant peptides by two donor 008 clones (18 and 20) (a and b) at an ET of 8
This study demonstrates that use of structural information improves the definition and optimization of cytotoxic T lymphocyte (CTL) epitopes. Epitope optimization usually requires numerous truncated peptides or a reverse immunogenetic approach, where the peptide binding motif is used to predict epitopes. These binding motifs do not reliably predict all peptides which are CTL epitopes. Comparison of 24 peptides eluted from HLA-B8 with 10 HLA-B8-restricted defined CTL epitopes demonstrated that known epitopes varied considerably at anchor positions. We used structural information based on determination of the crystal structure of the HLA-B8-GGKKKYKL complex to reassess previously described CTL epitopes, to predict new epitopes, and to predict the consequences of naturally occurring variation within epitopes. These predictions were confirmed by cytotoxicity and binding assays. Use of combined structural and immunological data more accurately defines the true peptide-binding motif of a restriction element
Virus-specific cytotoxic T-lymphocyte (CTL) responses are critical in the control of human immunodeficiency virus type 1 (HIV-1) infection and will play an important part in therapeutic and prophylactic HIV-1 vaccines. The identification of virus-specific epitopes that are efficiently recognized by CTL is the first step in the development of future vaccines. Here we describe the immunological characterization of a number of novel HIV-1-specific, HLA-A2-restricted CTL epitopes that share a high degree of conservation within HIV-1 and a strong binding to different alleles of the HLA-A2 superfamily. These novel epitopes include the first reported CTL epitope in the Vpr protein. Two of the novel epitopes were immunodominant among the HLA-A2-restricted CTL responses of individuals with acute and chronic HIV-1 infection. The novel CTL epitopes identified here should be included in future vaccines designed to induce HIV-1-specific CTL responses restricted by the HLA-A2 superfamily and will be important to
PubMed journal article Identification and characterization of a human agonist cytotoxic T-lymphocyte epitope of human prostate-specific antige were found in PRIME PubMed. Download Prime PubMed App to iPhone, iPad, or Android
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In the course of constructing a recombinant vaccinia virus encoding the influenza A nucleoprotein (NP) gene preceded by the hemagglutinin leader sequence, we isolated a single base-pair deletion mutant which gave rise to L+NP(1-159) in which only the first 159 amino acids were in frame. Despite this, when we infected target cells, we found that the point mutant was able to sensitize them for lysis not only by cytotoxic T cells recognizing residues 50-58 (the in-frame portion), but also by CTL to epitopes which are downstream of the mutation (366-374 and 378-386). Furthermore, normal C57BL/6 mice can be primed with the frameshift NP to recognize the immunodominant Db-restricted epitope 366-374 (which is out of frame). Experiments in which the mutant gene product was processed in the endoplasmic reticulum of target cells suggested that the apparent suppression occurred during polypeptide extension.
In the course of constructing a recombinant vaccinia virus encoding the influenza A nucleoprotein (NP) gene preceded by the hemagglutinin leader sequence, we isolated a single base-pair deletion mutant which gave rise to L+NP(1-159) in which only the first 159 amino acids were in frame. Despite this, when we infected target cells, we found that the point mutant was able to sensitize them for lysis not only by cytotoxic T cells recognizing residues 50-58 (the in-frame portion), but also by CTL to epitopes which are downstream of the mutation (366-374 and 378-386). Furthermore, normal C57BL/6 mice can be primed with the frameshift NP to recognize the immunodominant Db-restricted epitope 366-374 (which is out of frame). Experiments in which the mutant gene product was processed in the endoplasmic reticulum of target cells suggested that the apparent suppression occurred during polypeptide extension.
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The proteasome, an essential component of the ATP-dependent proteolytic pathway in eukaryotic cells, is responsible for the degradation of most cellular proteins and is believed to be the main source of MHC class I-restricted antigenic peptides for presentation to CTL. Inhibition of the proteasome by lactacystin or various peptide aldehydes can result in defective Ag presentation, and the pivotal role of the proteasome in Ag processing has become generally accepted. However, recent reports have challenged this observation. Here we examine the processing requirements of two HLA A*0201-restricted epitopes from HIV-1 reverse transcriptase and find that they are produced by different degradation pathways. Presentation of the C-terminal ILKEPVHGV epitope is impaired in ME275 melanoma cells by treatment with lactacystin, and is independent of expression of the IFN-gamma-inducible proteasome beta subunits LMP2 and LMP7. In contrast, both lactacystin treatment and expression of LMP7 induce the presentation of
The identification of class II binding peptide epitopes from autoimmune disease-related antigens is an essential step in the development of antigen-specific immune modulation therapy. In the case of type 1 diabetes, T cell and B cell reactivity to the autoantigen glutamic acid decarboxylase 65 (GAD65) is associated with disease development in humans and in nonobese diabetic (NOD) mice. In this study, we identify two DRB1*0401-restricted T cell epitopes from human GAD65, 274-286, and 115-127. Both peptides are immunogenic in transgenic mice expressing functional DRB1*0401 MHC class II molecules but not in nontransgenic littermates. Processing of GAD65 by antigen presenting cells (APC) resulted in the formation of DRB1*0401 complexes loaded with either the 274-286 or 115-127 epitopes, suggesting that these naturally derived epitopes may be displayed on APC recruited into pancreatic islets. The presentation of these two T cell epitopes in the islets of DRB1*0401 individuals who are at risk for type 1
Vaccines designed to stimulate CTL should be able to deliver protein antigens to the cytoplasm of host cells for processing and presentation by MHC-I. Many systems have been exploited to accomplish cytoplasmic delivery, including viral and bacterial vectors and DNA vaccines (7, 8, 14, 22, 27, 33, 36). There have also been reports demonstrating that antiviral immunity can be primed in mice vaccinated with a recombinant Bordetella adenylate cyclase toxin incorporating a CTL epitope from LCMV (11, 29, 31); however, the data demonstrated protection only when the recombinant toxin was injected in the presence of an adjuvant, aluminum hydroxide (29). Therefore, it remains unclear whether the antiviral protection was a result of toxin delivery or adjuvant activity. This report describes the use of a nontoxic, truncated form of anthrax toxin as an epitope delivery system without the use of adjuvant.. We demonstrate that protective immunity against a viral pathogen, LCMV, is generated in BALB/c mice ...
MHC-binding predictions have facilitated T cell epitope discovery by narrowing the search space to a manageable number of likely peptide candidates. Compared with approaches that do not use predictions, such as screening overlapping peptides, a downside of the prediction approach was that peptides of noncanonical lengths were missed (35). Naively, one could simply extend binding predictions to peptides of any length and rank all peptides based on their predicted affinity. But, as demonstrated in our study, although peptides of noncanonical lengths might have similar or even better predicted binding affinities than the canonical 9mer peptides, they end up being underrepresented among the naturally presented ligands eluted from MHC molecules and, consequently, are recognized less frequently by T cells. In this study, we explained these similarities between the length profiles of naturally presented peptides by fitting a common, underlying peptide-length distribution. This common length ...
The precise role played by HIV-specific cytotoxic T lymphocytes (CTL) in HIV infection remains controversial. Despite strong CTL responses being generated during the asymptomatic phase, the virus persists and AIDS ultimately develops. It has been argued that the virus is so variable, and the virus turnover so great that escape from CTL recognition would occur continually, but so far there is limited evidence for CTL escape. The opposing argument is that evidence for CTL escape is present but hard to find because multiple anti-HIV immune responses are acting simultaneously during the asymptomatic phase of infection. We describe six donors who make a strong CTL response to an immunodominant HLA-B27-restricted epitope. In the two donors who progressed to AIDS, CTL escape to fixation by the same mutation was observed, but only after 9-12 years of epitope stability. CTL escape may play an important role in the pathogenesis of HIV infection.
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In this study we show that the HPV16 E7-specific CD8+ T cell response is far more vigorous after vaccination with a HPV16 E7-derived 35-residue long peptide than following vaccination with the minimal CTL epitope. Our data suggest that two distinct DC-related mechanisms lie at the basis of this result. First, the long peptide contains both a CTL epitope and a Th epitope. Prime-boost vaccinations of wild-type, MHC class II−/−, and CD40−/− mice show that the CD40-CD40L interactions between APC and E7-specific Th cells contribute considerably to the level of the CD8+ T cell response. Second, under circumstances excluding T cell help, a comparison of the CD8+ T cell responses induced by either the minimal CTL epitope (nine residues) or the long peptide combined with DC-activating agents demonstrates that vaccination with the long peptide results in far better responses. This suggests that compared with the short minimal CTL epitope the long peptide is much better presented by professional ...
A long-standing question in the field of immunology concerns the factors that contribute to Th cell epitope immunodominance. For a number of viral membrane proteins, Th cell epitopes are localized to exposed protein surfaces, often overlapping with Ab binding sites. It has therefore been proposed that Abs on B cell surfaces selectively bind and protect exposed protein fragments during Ag processing, and that this interaction helps to shape the Th cell repertoire. While attractive in concept, this hypothesis has not been thoroughly tested. To test this hypothesis, we have compared Th cell peptide immunodominance in normal C57BL/6 mice with that in C57BL/6( micro MT/ micro MT) mice (lacking normal B cell activity). Animals were first vaccinated with DNA constructs expressing one of three different HIV envelope proteins, after which the CD4(+) T cell response profiles were characterized toward overlapping peptides using an IFN-gamma ELISPOT assay. We found a striking similarity between the peptide ...
We recently discover a new immune escape mechanism that may help viruses escape from immune detection, which might compromise vaccine efficacy. Viruses that cause chronic infection in human contain higher numbers of T cell epitopes whose TCR-facing amino acids are identical to those of numerous peptides from the human proteome. We postulate that viruses that incorporate such human-like epitopes may exploit host tolerance to avoid or suppress effector responses. In order to predict these human-like epitopes, we developed an immunoinformatics tool, JanusMatrix.. Using JanusMatrix, we have identified T cell epitopes in H7N9 influenza HA protein that are highly conserved with human genome epitopes, and these epitopes possess low immunogenicity, activate natural Tregs and suppress bystander effector T cell responses in vitro. The human like T cell epitopes may contribute to the delayed, low titer of H7N9 hemagglutination inhibiting antibody responses and diminished seroconversion rates that have been ...
This graph shows the total number of publications written about Immunodominant Epitopes by people in this website by year, and whether Immunodominant Epitopes was a major or minor topic of these publications ...
The Experimental Analysis of Mutlitple Computationally-Driven Methods for the Deletion of Broadly Distributed T cell Epitopes in a Functional Biotherapeutic Candidate A Thesis Submitted to the Faculty in partial fulfillm ent o f the requirements for the degree of D octor o f Philosophy by Regina Salvat Thayer School o f Engineering D artmouth College Hanover, N ew Hampshire January 4, 2015 Chairman Exam ining Committee: Professor Karl Griswold M em ber Professor M argaret Ackerman M em ber Professor Chris Bailey-Kellogg M emb er___________________________ Professor Lenny M oise F. Jon Kull Dean o f Graduate Studies ...
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Fingerprint Dive into the research topics of TAP-independent presentation of CTL epitopes by Trojan antigens. Together they form a unique fingerprint. ...
Peptide tools for target & epitope discovery, development of treatment & diagnosis of allergies, such as food allergy, atopic dermatitis, allergic asthma…
Rational design of immunotherapeutics relies on clear knowledge of the immunodominant epitopes of antigens. Current methods for identifying kinetically stable peptide-MHC complexes are in many cases i
Peptides that combine poorly to MHC course We substances elicit low functional avidity Capital t cell reactions often. immune system reactions can become increased towards Capital t cell epitopes with low practical avidity by raising antigen denseness. We also determined a heteroclitic epitope (RCVIFANI) that elicited a Capital t cell response with almost full cross-reactivity with indigenous epitope and proven improved MHC-peptide plethora likened to indigenous S i9000598. Structural and thermal dissolve studies indicated that the Queen600V replacement improved balance of the peptide-MHC complicated without significantly changing the antigenic surface area, causing in cross-reactive Big t cell reactions extremely. Our data high light that improved pMHC Rabbit polyclonal to IL25 complicated screen contributes to heteroclitic epitope effectiveness and explain guidelines for increasing immune system reactions that cross-react with the indigenous epitope. Intro growth and Virus distance both ...
T cells play pivotal roles in shaping host immune responses in infectious diseases, autoimmunity and cancer. The activation of T cells requires immune and growth factor-derived signals. However, alterations in nutrients and metabolic signals tune T cell responses by impinging upon T cell fates and immune functions. In this review, we summarize how key nutrients, including glucose, amino acids and lipids, and their sensors and transporters shape T cell responses. We also briefly discuss regulation of T cell responses by oxygen and energy sensing mechanisms.
Analysis of cytotoxic T cell epitopes in relation to cancer. / Stranzl, Thomas; Brunak, Søren (Main supervisor); Larsen, Mette Voldby (Supervisor).. Kgs. Lyngby : Technical University of Denmark (DTU), 2012. 97 p.. Publication: Research › Ph.D. thesis - Annual report year: 2012 ...
In this study we characterized the CTL response induced in vivo against TS/A mouse adenocarcinoma cells genetically engineered to express different cytokine or costimulatory molecules, i.e., IFN-α, IFN-γ, IL-4, and B7.1. Independent of the molecule introduced, the CTL response elicited was constantly directed against a single immunodominant epitope represented by the AH1 peptide derived from the gp70 product of an endogenous MuLV and corresponding to amino acids 423-431 of the protein (19) . Indeed, tumor rejection was accompanied by increases in a CD8+ T-cell population that was stainable with gp70-specific tetramers; moreover, independent in vitro restimulation of splenocytes from mice that had rejected a primary TS/A tumor challenge with either gp70423-431 peptide or engineered TS/A, which provided the entire antigenic array of the tumor cells, produced a similar large increase in CTLs specifically recognizing the AH1 antigenic epitope. Finally, MLTC lytic activity could be inhibited in an ...
Authors: AI Webb, MA Dunstone, WS Chen, MI Aguilar, QY Chen, H Jackson, L Chang, L Kjer-Nielsen, T Beddoe, J McCluskey, J Rossjohn, AW Purcell
هدف از پژوهش حاضر بررسی نقش میانجی اهداف پیشرفت در رابطه بین نیاز به خاتمه و درگیری شناختی بر حسب تعلل‌ورزی دانش‌آموزان بود. برای این منظور 268 نفر (161 دختر و 107 پسر) از دانش‌آموزان پایه سوم دبیرستان‌های دولتی شهر شیراز به روش نمونه‌گیری خوشه‌ای چند مرحله‌ای انتخاب شدند و به پرسشنامه‌ای خودگزارشی متشکل از خرده مقیاس-های نیاز به خاتمه (NFCS)، مقیاس اهداف پیشرفت (AGS)، مقیاس درگیری شناختی (MSLQ) و مقیاس تعلل‌ورزی تحصیلی (PASS) پاسخ دادند. نتایج پژوهش بطور کل‍‍ی نشان داد که در یک بافت تحصیلی تعلل‌ورزی، ابعاد نیاز به خاتمه از طریق واسطه‌گری اهداف پیشرفت بر راهبردهای
"Mapping and characterization of visna/maedi virus cytotoxic T-lymphocyte epitopes". J. Gen. Virol. 89 (Pt 10): 2586-96. doi: ... This causal lentivirus can be found in monocytes, lymphocytes and macrophages of infected sheep in the presence of humoral and ... Infected differentiated monocytes, also known as macrophages, will continuously present VMV antigens inducing T-lymphocytes to ... visna virus does not infect T-lymphocytes. The relationship of visna and HIV as lentiviruses was first published in 1985 by ...
In RHD, molecular mimicry results in incorrect T cell activation, and these T lymphocytes can go on to activate B cells, which ... Molecular mimicry occurs when epitopes are shared between host antigens and Streptococcus antigens. This causes an autoimmune ... The valvular endothelium is a prominent site of lymphocyte-induced damage. CD4+ T cells are the major effectors of heart tissue ... The dominant contributors are a component of MHC class II molecules, found on lymphocytes and antigen-presenting cells, ...
The TCRs of T lymphocytes recognise only sequential epitopes, also called linear epitopes, of only peptides and only if coupled ... It presents epitopes to killer T cells, also called cytotoxic T lymphocytes (CTLs). A CTL expresses CD8 receptors, in addition ... Classical MHC molecules present epitopes to the TCRs of CD8+ T lymphocytes. Nonclassical molecules (MHC class IB) exhibit ... T lymphocytes can detect a peptide displayed at 0.1%-1% of the MHC molecules. In their development in the thymus, T lymphocytes ...
2006). "A molecular approach to the identification of cytotoxic T-lymphocyte epitopes with Equine Herpes-1". Journal of General ...
"The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides". ... Bowness, Paul (1993). Recognition of antigen and superantigen by cytotoxic lymphocytes (Thesis). Thesis DPhil--University of ... "Vertical T cell immunodominance and epitope entropy determine HIV-1 escape". The Journal of Clinical Investigation. 123 (1): ... "Phenotypic analysis of antigen-specific T lymphocytes". Science. 274 (5284): 94-96. Bibcode:1996Sci...274...94A. doi:10.1126/ ...
It targets CD20 marker on B lymphocytes and hence is an immunosuppressive drug. Ocrelizumab binds to an epitope that overlaps ... Ocrelizumab is a humanized monoclonal antibody that binds to a CD20 epitope that overlaps partially with the epitope to which ... with the epitope to which rituximab binds. It was approved by the U.S. Food and Drug Administration (FDA) in March 2017, and ...
"IFN-gamma exposes a cryptic cytotoxic T lymphocyte epitope in HIV-1 reverse transcriptase". Journal of Immunology. 162 (12): ... Madani N, Kabat D (Dec 1998). "An endogenous inhibitor of human immunodeficiency virus in human lymphocytes is overcome by the ... is the processing of numerous MHC class-I restricted T cell epitopes. This gene encodes a member of the proteasome B-type ... is the major degradation machinery that degrades the antigen and present the resulting peptides to cytotoxic T lymphocytes. The ...
GP2 consisting of 9 amino acids is the subdominant epitope. Both E75 and GP2 stimulate the CD8+ lymphocytes but GP2 has a lower ... Some IgE-inducing epitopes cause hypersensitivity reactions after vaccination in humans due to the overlap with IgG epitopes in ... The whole peptide vaccine is to mimic the epitope of an antigen, so epitope design is the most important stage of vaccine ... The followings are the points to consider when designing the epitope: The non-dominant epitope could generate a stronger immune ...
3 HLA-A2 restricted epitopes in CTAG1B were identified as the recognition sites for CD8+ cytotoxic T lymphocytes. Integrated ... A2-binding peptide epitopes". The Journal of Experimental Medicine. 187 (2): 265-70. doi:10.1084/jem.187.2.265. PMC 2212106. ... "NY-ESO-1 119-143 is a promiscuous major histocompatibility complex class II T-helper epitope recognized by Th1- and Th2-type ... "Efficient simultaneous presentation of NY-ESO-1/LAGE-1 primary and nonprimary open reading frame-derived CTL epitopes in ...
... encoding the interleukin 1 receptor antagonist and six epitopes recognized by human cytolytic T lymphocytes". Cancer Res. 60 ( ...
... cytotoxic T-lymphocyte responses against dominant and recessive epitopes of influenza virus nucleoprotein induced by DNA ... CTL responses can be raised against immunodominant and immunorecessive CTL epitopes, as well as subdominant CTL epitopes,[ ... One of the advantages of DNA vaccines is that they are able to induce cytotoxic T lymphocytes (CTL) without the inherent risk ... This may prove to be a useful tool in assessing CTL epitopes and their role in providing immunity. Cytotoxic T-cells recognise ...
"Amphipathic segment of the nicotinic receptor alpha subunit contains epitopes recognized by T lymphocytes in myasthenia gravis ...
The parts of an antigen that interact with an antibody molecule or a lymphocyte receptor, are called epitopes, or antigenic ... T and B lymphocytes are the cells of the adaptive immune system. The human body has about 2 trillion lymphocytes, which are 20- ... In jawless fishes, two subsets of lymphocytes use variable lymphocyte receptors (VLRs) for antigen binding. Diversity is ... Lymphocyte receptors, Ig and TCR, are found in all jawed vertebrates. The most ancient Ig class, IgM, is membrane-bound and ...
Lymphocyte anergy pathways involve induction of some, but not all of the signaling pathways used during lymphocyte activation. ... demonstrated that epitope-mapping tools could accurately identify the epitopes responsible for 95% of the murine T-cell ... It may have been expected that B lymphocytes and T lymphocytes would cluster separately from each other, or that natural killer ... T-cell and B-cell epitope mapping algorithms can computationally predict epitopes based on the genomic sequence of pathogens, ...
... containing a mutated epitope recognized by autologous tumor-infiltrating T lymphocytes". J. Immunol. 166 (4): 2871-7. doi: ...
The SART1(259) protein possesses tumor epitopes capable of inducing HLA-A2402-restricted cytotoxic T lymphocytes in cancer ... "A gene encoding antigenic peptides of human squamous cell carcinoma recognized by cytotoxic T lymphocytes". J Exp Med. 187 (3 ... "Identification of a SART-1-derived peptide capable of inducing HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes". ... required for induction of histocompatibility leukocyte antigen-class I-restricted and tumor-specific cytotoxic T lymphocytes by ...
"The antigen-specific induction of normal human lymphocytes in vitro is down-regulated by a conserved HIV p24 epitope". Immunol ... Sewell WA, Brown MH, Dunne J, Owen MJ, Crumpton MJ (1986). "Molecular cloning of the human T-lymphocyte surface CD2 (T11) ... It interacts with other adhesion molecules, such as lymphocyte function-associated antigen-3 (LFA-3/CD58) in humans, or CD48 in ... Schraven B, Samstag Y, Altevogt P, Meuer SC (1990). "Association of CD2 and CD45 on human T lymphocytes". Nature. 345 (6270): ...
... the differentiated DCs present the allergenic epitope associated with the allergen to T lymphocytes. These T cells then divide ... In a similar fashion, cytotoxic T lymphocytes patrol an area of skin and play an important role in controlling both the ... Their immunology centres on the interaction of immunoregulatory cytokines and discrete subpopulations of T lymphocytes. The ... and present the antigen to T-lymphocytes. This process is controlled by cytokines and chemokines - with tumor necrosis factor ...
"The antigen-specific induction of normal human lymphocytes in vitro is down-regulated by a conserved HIV p24 epitope". ... Implications for the relationship of NK and T lymphocytes". Journal of Immunology. 149 (6): 1876-80. PMID 1387664. Wong S, ... "A synthetic peptide with sequence identity to the transmembrane protein GP41 of HIV-1 inhibits distinct lymphocyte activation ... "Modulation of CD4 lateral interaction with lymphocyte surface molecules induced by HIV-1 gp120". European Journal of Immunology ...
Vaccination with cytotoxic T lymphocyte epitope‐containing peptide protects against a tumor induced by human papillomavirus ... In addition, it is likely that protein vaccination leads to presentation of epitopes in the context of various HLA alleles, and ... Cooperation between helper T cells and cytotoxic T lymphocyte precursors. Annals of the New York Academy of Sciences, 532(1), ... The inclusion of CD4+ epitopes into MAGE-3 vaccination studies has recently been facilitated by the identification of several ...
2006). "Profiling lymphocyte subpopulations in peripheral blood under efalizumab treatment of psoriasis by multi epitope ligand ... The Toponome Imaging Systems (TIS) and multi-epitope-ligand cartographs (MELC) represent different stages of the ICM ... Ademmer; Ebert; Müller-Ostermeyer; Friess; Büchler; Schubert; Malfertheiner (April 1998). "Effector T lymphocyte subsets in ... "Comparative Multi-Epitope-Ligand-Cartography reveals essential immunological alterations in Barrett's metaplasia and esophageal ...
Epitope spreading or epitope drift - when the immune reaction changes from targeting the primary epitope to also targeting ... In this form of the disease, the absence of lymphocytes can accelerate organ damage, and intravenous IgG administration can be ... Epitope modification or Cryptic epitope exposure - this mechanism of autoimmune disease is unique in that it does not result ... Pike B, Boyd A, Nossal G (1982). "Clonal anergy: the universally anergic B lymphocyte". Proceedings of the National Academy of ...
1992). "The antigen-specific induction of normal human lymphocytes in vitro is down-regulated by a conserved HIV p24 epitope". ... 1996). "Composition of TCR-CD3 complex in human intestinal intraepithelial lymphocytes: lack of Fc epsilon RI gamma chain". Int ... 1989). "Dephosphorylation of the human T lymphocyte CD3 antigen". Eur. J. Biochem. 181 (1): 55-65. doi:10.1111/j.1432-1033.1989 ... "A synthetic peptide with sequence identity to the transmembrane protein GP41 of HIV-1 inhibits distinct lymphocyte activation ...
1992). "The antigen-specific induction of normal human lymphocytes in vitro is down-regulated by a conserved HIV p24 epitope". ... 1987). "The human T3 gamma chain is phosphorylated at serine 126 in response to T lymphocyte activation". J. Biol. Chem. 262 ( ... Implications for the relationship of NK and T lymphocytes". J. Immunol. 149 (6): 1876-80. PMID 1387664. Letourneur F, Klausner ... 1989). "Dephosphorylation of the human T lymphocyte CD3 antigen". Eur. J. Biochem. 181 (1): 55-65. doi:10.1111/j.1432-1033.1989 ...
... ic escape Antitoxin Conformational epitope Epitope Linear epitope Magnetic immunoassay Neutralizing antibody Original ... Upon exposure to an antigen, only the lymphocytes that recognize that antigen are activated and expanded, a process known as ... Using the "lock and key" metaphor, the antigen can be seen as a string of keys (epitopes) each of which matches a different ... Any such feature constitutes an epitope. Most antigens have the potential to be bound by multiple antibodies, each of which is ...
This antigen possesses tumor epitopes capable of inducing HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes in ... of a gene coding for a protein possessing shared tumor epitopes capable of inducing HLA-A24-restricted cytotoxic T lymphocytes ...
There is a large diversity of epitopes recognized and, as a result, it is possible for some B and T lymphocytes to develop with ... Each of these lymphocytes express specificity to a particular epitope, or the part of an antigen to which B cell and T cell ... this allows microorganisms with epitopes similar to host antigen to escape recognition and detection by T and B lymphocytes. ... B and T lymphocytes are tested for their affinity for self MHC/peptide complexes before leaving the primary lymphoid organs and ...
MECA-79 mAb inhibits lymphocyte emigration through HEVs into lymph nodes in vivo and lymphocyte adhesion to lymph node and ... The MECA-79 carbohydrate epitope decorates a family of HEV counter-receptors for L-selectin, both in mouse and human16. Another ... This illustrates the function of HEVs in lymphocyte recruitment, and explains why these vessels were implicated in lymphocyte ... express specialized ligands for lymphocytes and are able to support high levels of lymphocyte extravasation). HEVs enable naïve ...
Distinct but overlapping epitopes are involved in alpha 4 beta 7-mediated adhesion to vascular cell adhesion molecule-1, ... and lymphocyte aggregation". Journal of Immunology. 153 (9): 3847-61. PMID 7523506. as referenced in paragraph 146 of the PCT ... "Distinct but overlapping epitopes are involved in alpha 4 beta 7-mediated adhesion to vascular cell adhesion molecule-1, ... mucosal addressin-1, fibronectin, and lymphocyte aggregation. Andrew DP, Berlin C, Honda S, Yoshino T, Hamann A, Holzmann B, ...
... cytotoxic T lymphocyte epitope in a human glioma-associated antigen, interleukin 13 receptor alpha2 chain". Clinical Cancer ...
2] Innate lymphocytes-lineage, localization and timing of differentiation. Further reading[edit]. *Cell-Mediated Immunity. ... activating antigen-specific cytotoxic T cells that are able to induce apoptosis in body cells displaying epitopes of foreign ... Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of ... "Innate lymphocytes-lineage, localization and timing of differentiation". Cellular & Molecular Immunology. 16 (7): 627-633. doi ...
"Direct determination of the interleukin-6 binding epitope of the interleukin-6 receptor by NMR spectroscopy". The Journal of ... macrophage inhibitory factor directs the accumulation of interleukin-17-producing tumor-infiltrating lymphocytes and predicts ...
The parts of an antigen that interact with an antibody molecule or a lymphocyte receptor, are called epitopes, or antigenic ... LymphocytesEdit. Main article: Lymphocyte. T and B lymphocytes are the cells of the adaptive immune system. The human body has ... In jawless fishes, two subsets of lymphocytes use variable lymphocyte receptors (VLRs) for antigen binding.[33] Diversity is ... CD8+ T lymphocytes and cytotoxicityEdit. Main article: Cytotoxic T cell. Cytotoxic T cells (also known as TC, killer T cell, or ...
Lymphocyte T-Cell Immunomodulator is a potent regulator of CD-4 lymphocyte production and function.[16] It has been shown to ... a characteristic that scientists believe may mask the B-cell epitopes of the Env glycoprotein giving the virus resistance to ... FIV compromises the immune system of cats by infecting many cell types, including CD4+ and CD8+ T lymphocytes, B lymphocytes, ... Lymphocyte T-Cell Immunomodulator is intended as an aid in the treatment of cats infected with feline leukemia virus (FeLV) and ...
To obtain antibody that is specific for a single epitope of an antigen, antibody-secreting lymphocytes are isolated from the ... The B lymphocyte, in this ready-to-respond form, is known as a "naive B lymphocyte." The naive B lymphocyte expresses both ... Each Ig unit (labeled 1) has two epitope binding Fab regions, so IgM is capable of binding up to 10 epitopes. ... The antibody's paratope interacts with the antigen's epitope. An antigen usually contains different epitopes along its surface ...
... also called adoptive immunization which involves the transfer of mature circulating lymphocytes. It is rarely used in humans, ...
... odnose se na promjene ili nedostatak istog između antitijela koja ciljaju različite epitope). Kako se varijabilna regija ne ... "Interleukin-10 induces immunoglobulin G isotype switch recombination in human CD40-activated naive B lymphocytes". The Journal ...
The molecule's positive charge allows for binding to phospholipids and cardiolipin, both of which can be found as epitopes on ... Donlon TA, Krensky AM, Clayberger C (1990). "Localization of the human T lymphocyte activation gene 519 (D2S69E) to chromosome ... Krensky AM (February 2000). "Granulysin: a novel antimicrobial peptide of cytolytic T lymphocytes and natural killer cells". ... Dotiwala F, Lieberman J (October 2019). "Granulysin: killer lymphocyte safeguard against microbes". Current Opinion in ...
B lymphocyte precursors) and CD34+ megakaryocytes. Cells observed as CD34+ and CD38- are of an undifferentiated, primitive form ... "Complexity and differential expression of carbohydrate epitopes associated with L-selectin recognition of high endothelial ...
Brown MJ, Hallam JA, Liu Y, Yamada KM, Shaw S (July 2001). "Cutting edge: integration of human T lymphocyte cytoskeleton by the ... Thirdly, an insert of five amino acids in the fifteenth spectrin motif bears a highly antigenic epitope resembling an ankyrin- ... Gregorio CC, Repasky EA, Fowler VM, Black JD (1994). "Dynamic properties of ankyrin in T lymphocytes: colocalization with ...
Also, the fucosylated triantennary N-glycans were shown to have the fucose as part of a so-called Sialyl Lewis x epitope, which ... This suggests a role for α1PI not only in locomotion of lymphocytes through tissue, but as a consequence of infection, a ... Besides limiting elastase activity to limit tissue degradation, A1PI also acts to induce locomotion of lymphocytes through ...
For example, lymphocyte proliferation can be measured this way in lymphoproliferative disorders. Bromodeoxyuridine (BrdU) is ... which is less harsh than the conditions used to expose the epitope for BrdU antibodies. Edoxudine is an antiviral drug. ...
Minor lymphocyte stimulating (Mls) exotoxins were originally discovered in the thymic stromal cells of mice. These toxins are ... 2003). "Identification of the Antigenic Epitopes in Staphylococcal Enterotoxins A and E and Design of a Superantigen for Human ... Watson AR, Lee WT (August 2006). "Defective T cell Receptor-mediated Signal Transduction in Memory CD4 T Lymphocytes Exposed to ... The large number of activated T-cells generates a massive immune response which is not specific to any particular epitope on ...
Erns severely reduced the protein synthesis of various kinds of lymphocytes without causing cell membrane damage. Symptoms of ... After viral infection, NS4B can trigger humoral and cellular immune responses thanks to its highly conserved epitopes. NS5B ( ... which regulates cell tropism by interacting with cell surface receptors and inducing responses from cytotoxic T-lymphocytes and ...
Most often the lymphocyte count is greater than 5000 cells per microliter (µl) of blood but can be much higher. The presence of ... Deans JP, Polyak MJ (February 2008). "FMC7 is an epitope of CD20". Blood. 111 (4): 2492, author reply 2493-2492, author reply ... Normal B lymphocytes consist of a stew of different antibody-producing cells, resulting in a mixture of both kappa- and lambda- ... CLL results in the buildup of B cell lymphocytes in the bone marrow, lymph nodes, and blood. These cells do not function well ...
Activating and blocking antibodies mostly bind to conformational epitopes, whereas neutral antibodies bind to linear epitopes. ... The majority of anti-TPO antibodies are produced by thyroid infiltrating lymphocytes, with minor contributions from lymph nodes ... Most antibodies produced are directed to conformational epitopes of the immunogenic carboxyl-terminal region of the TPO protein ... causing infiltration of lymphocytes. This inflammatory response leads to cytokine production that causes fibroblasts to produce ...
EPD uses dilutions of allergen and an enzyme, beta-glucuronidase, to which T-regulatory lymphocytes are supposed to respond by ... "Specificity of IgE antibodies to sequential epitopes of hen's egg ovomucoid as a marker for persistence of egg allergy". ... This is due to the migration of other leukocytes such as neutrophils, lymphocytes, eosinophils, and macrophages to the initial ... These TH2 cells interact with other lymphocytes called B cells, whose role is production of antibodies. Coupled with signals ...
Antigen uptake by T-lymphocytes is enhanced when a given antigen is processed in the presence of tuftsin. Maximal effect was ... Conjugates with polytuftsin retain tuftsin-like effects and increase the epitope specific antibody production. Tuftsin sequence ... Extensive augmentation of white blood counts and enhanced cytotoxicity of lymphocytes was notable. No detectable tuftsin- ...
These molecules may be recognized by CD8+ cytotoxic T lymphocytes as foreign neoepitopes and, with the help of CD4+ T ... "Mutant MHC class II epitopes drive therapeutic immune responses to cancer". Nature. 520 (7549): 692-696. Bibcode:2015Natur.520 ... lymphocytes, trigger an immune response leading to tumor-specific killing. CD8+ T cells are specialized for direct tumor cell ...
... and B-lymphocytes). Normally, these APC 'present' class II receptor/antigens to a great many T-cells, each with unique T-cell ... of the disease by antibodies against the MHC peptide region involved in the presentation of a pathogenic T-cell epitope". Crit ...
The spleen, mesenteric lymph nodes, Peyer's patches, and lamina propria lymphocytes induce a strong Th2 immune response by ... polygyrus Elicits a Dominant Nonprotective Antibody Response Directed against Restricted Glycan and Peptide Epitopes". The ...
Those peptides expressing a drug-related, non-self epitope on their HLA-A, HLA-B, HLA-C, HLA-DM, HLA-DO, HLA-DP, HLA-DQ, or HLA ... Laboratory findings include increased blood eosinophil and atypical lymphocyte counts, elevated blood markers for systemic ... The drug or metabolite covalently binds with a host protein to form a non-self, drug-related epitope. An antigen-presenting ... Importantly, however, non-self epitopes must bind to specific HLA serotypes in order to stimulate T cells. Since the human ...
This activity is required to generate signal sequence-derived human lymphocyte antigen-E epitopes that are recognized by the ... 2002). "Intramembrane proteolysis of signal peptides: an essential step in the generation of HLA-E epitopes". J. Immunol. 167 ( ...
Removal of sialic acid residues from the surface of tumor cells makes them available to NK cells and cytotoxic T lymphocytes ... Portner A, Scroggs RA, Naeve CW (April 1987). "The fusion glycoprotein of Sendai virus: sequence analysis of an epitope ... SeV activates natural killer cells (NK), cytotoxic T lymphocytes (CTL) and dendritic cells (DC). The secretion of interleukin-6 ... Macher BA, Beckstead JH (1990-01-01). "Distribution of VIM-2 and SSEA-1 glycoconjugate epitopes among human leukocytes and ...
2004)‎. Induction of Cytotoxic T Lymphocytes by Immunization with Dengue Virus - Derived, Modified Epitope Peptide, Using ... Induction of Cytotoxic T Lymphocytes by Immunization with Dengue Virus - Derived, Modified Epitope Peptide, Using Dendritic ...
Identification of a tyrosinase epitope recognized by HLA-A24-restricted, tumor-infiltrating lymphocytes. ... Dive into the research topics of Identification of a tyrosinase epitope recognized by HLA-A24-restricted, tumor-infiltrating ...
Functional compensation of a detrimental amino acid substitution in a cytotoxic-T-lymphocyte epitope of influenza a viruses by ... Functional compensation of a detrimental amino acid substitution in a cytotoxic-T-lymphocyte epitope of influenza a viruses by ... Functional compensation of a detrimental amino acid substitution in a cytotoxic-T-lymphocyte epitope of influenza a viruses by ... title = "Functional compensation of a detrimental amino acid substitution in a cytotoxic-T-lymphocyte epitope of influenza a ...
One mechanism reported to regulate the proliferative capacity of activated lymphocytes is mediated by the effect of telomerase ... CD8-Positive T-Lymphocytes / virology* * Cell Division / immunology * Enzyme Induction / immunology * Epitopes, T-Lymphocyte / ... One mechanism reported to regulate the proliferative capacity of activated lymphocytes is mediated by the effect of telomerase ...
The first human RSV-specific cytotoxic T-lymphocyte epitope to be defined is described. This HLA B7-restricted epitope in ... The first human RSV-specific cytotoxic T-lymphocyte epitope to be defined is described. This HLA B7-restricted epitope in ... Characterization of a novel respiratory syncytial virus-specific human cytotoxic T-lymphocyte epitope. ... Adult, Enzyme-Linked Immunosorbent Assay, Epitopes, T-Lymphocyte, Flow Cytometry, HLA-B7 Antigen, Humans, Respiratory Syncytial ...
Original antigenic sin impairs cytotoxic T lymphocyte responses to viruses bearing variant epitopes. Nature. 1998;394:482-5. ... Original antigenic sin: a bone marrow-derived lymphocyte memory phenomenon modulated by thymus-derived lymphocytes. J Exp Med. ... with ongoing selection and expansion of lymphocyte clones that have increasing antibody avidity at key cross-reactive epitopes ... 7-10) and possibly with epitope competition between naïve and antigen-specific B cells (8). A phenomenon analogous to original ...
2.T-lymphocytes are the key responding cellular elements of the immune response to M. tuberculosis. These cells should be ... This should permit amino acid analysis and synthesis of epitopes which may be useful for serologic or skin-test diagnosis. ... A related area to be explored is the study of the T-lymphocyte antigen receptor. Conclusion There is an urgent need for ... High priority should be placed on the search for genus- and species-specific epitopes. 2.DNA probes specific for M. ...
A related area to be explored is the study of the T-lymphocyte antigen receptor. Conclusion. There is an urgent need for ... This should permit amino acid analysis and synthesis of epitopes which may be useful for serologic or skin-test diagnosis. * T- ... High priority should be placed on the search for genus- and species-specific epitopes. * DNA probes specific for M. ... Systems that would assay material produced by the diseased hosts lymphocytes or macrophages might be useful for diagnosis. ...
KEY WORDS: Computational biology; B-lymphocyte epitopes; Recombinant fusion proteins; Antigenic variation; Mycoplasma hominis ... After excluding non-specific epitopes, the remaining peptides were further analyzed by the BepiPred Linear Epitope Prediction ... METHODS: The linear epitopes of P120 and P80 were predicted by the Kolaskar and Tongaonkar Antigenicity method. ... This study was conducted to predict and evaluate appropriate epitopes of two membrane proteins, P120 and P80, by bioinformatics ...
T-Lymphocyte Epitopes 7% * tapasin 16% * Textbooks 11% * Vertebrates 17% * Viral Genes 7% ...
Autoreactive B lymphocytes, which are normally inactive, become active in SLE because of a malfunction of normal homeostatic ... Other autoantibodies, including anti-dsDNA antibodies, develop through a process of epitope spreading. These autoantibodies ... Reduced B lymphocyte and immunoglobulin levels after atacicept treatment in patients with systemic lupus erythematosus: results ... Belimumab, an anti-B-lymphocyte stimulator [BLyS] monoclonal antibody, which is approved for treatment of adults with active ...
Mice received 106 epitope-specific T cells intravenously. FACS staining was performed on CLN-derived lymphocytes 5 d post- ... 2000) Neuronal FasL induces cell death of encephalitogenic T lymphocytes. Brain Pathol 10:353-364. doi:10.1111/j.1750-3639.2000 ... Lymphocytes (106) from pooled lymph node preparation from OT-I Thy1.1 and OT-II Thy1.1 transgenic mice were adoptively ... Lymphocyte isolation, and FACS.. Mice were deeply anesthetized with isoflurane and then transcardially perfused with cold PBS. ...
A degenerate HLA-DR epitope pool of HER-2/neu reveals a novel in vivo immunodominant epitope, HER-2/neu88-102. Karyampudi, L., ... Enzymatic discovery of a HER-2/neu epitope that generates cross-reactive T cells. Henle, A. M., Erskine, C. L., Benson, L. M., ... Clonal diversity of the T-cell population responding to a dominant HLA-A2 epitope of HER-2/neu after active immunization in an ... An HLA-DR-degenerate epitope pool detects insulin-like growth factor binding protein 2-specific immunity in patients with ...
The compound is a chimeric mAb targeting an epitope on the CD20 antigen found on B lymphocytes. ...
The development of CD8+ T-cell-based vaccine against HIV-1 has focused on searching for immunodominant epitopes. However, the ... 01+ individuals were stimulated with the mutated and wild-type peptides derived from the GC9 and SL9 epitopes. The functional ... 01+ individuals were stimulated with the mutated and wild-type peptides derived from the GC9 and SL9 epitopes. The functional ... the strong immune pressure of CD8+ T-cells causes the selection of viral variants with mutations in immunodominant epitopes. ...
Immunogenic lipopeptides comprising T-helper and cytotoxic T-lymphocyte (CTL) epitopes. David Jackson, Weiguang Zeng. ...
Enhancement of MHC class I binding and immunogenic properties of the CTL epitope peptides derived from dengue virus NS3 protein ... The immunogenecity of the defined H-2Kd-restricted, murine cytotoxic T lymphocyte (‎CTL)‎ epitopesof dengue viruses were ... examined for CTL induction in epitope peptide / H-2Kd tetramer assays. Thepeptides used in the study ... ...
Tedopi®, 10 combined neo-epitopes to induce a specific T lymphocyte activation. Phase III trial in advanced NSCLC: after ... Increased dendritic cell tumor-antigen specific presentation to T lymphocytes, leading to long-term anti-tumor memory immune ...
... the antigen-specific TCR repertoire is restricted by its peptide epitope and the presenting major histocompatibility complex ( ... Large numbers of dysfunctional CD8+ T lymphocytes bearing receptors for a single dominant CMV epitope in the very old. J. Clin ... If the number of structural solutions of a TCR to a given epitope is finite, it is intuitive that clonotypes would re-occur, ... Starr, S.E.; Allison, A.C. Role of T lymphocytes in recovery from murine cytomegalovirus infection. Infect. Immun. 1977, 17, ...
Journal Article] Identification of EphB6 variant-derived epitope peptides recognized by cytotoxic T-lymphocytes from HLA-A24^+ ... Journal Article] EphB6 variant-derived peptides with the ability to induce glioma-reactive cytotoxic T lymphocytes in HLA-A2+ ... Kinesin superfamily protein-derived peptides with the ability to induce glioma-reactive cytotoxic T lymphocytes in HLA-A24^+ ...
This activity is required to generate signal sequence-derived human lymphocyte antigen-E epitopes that are recognized by the ... Preproinsulin signal peptide epitopes are processed by SPP and loaded for HLA-guided immune recognition via pathways that are ...
Small TAg+ HCC recur in the presence of epitope-specific functional cytotoxic T lymphocytes. A, All mice depicted in ... Small TAg+ HCC recur in the presence of epitope-specific functional cytotoxic T lymphocytes. A, All mice depicted in ... Quantitation of CD8(+) T-lymphocyte responses to multiple epitopes from simian virus 40 (SV40) large T antigen in C57BL/6 mice ... ERAP1 regulates presentation of the subdominant epitope TAg-I and dominant epitope TAg-IV on TAg-driven primary HCC. A and B, ...
This antibodys epitope is resistant to digestion by trypsin and chymotrypsin. This MAb selectively interferes with lymphocyte ... This protein participates in a wide variety of cellular functions including lymphocyte activation, recirculation and homing, ...
Immunodominant T-cell epitope on the F protein of respiratory syncytial virus recognized by human lymphocytes. , ... Multi Epitope-based Vaccine Design for Protection , AABC. , 5 days ago. , Article Details , Related Articles , ... Human neutralizing antibodies to cold linear epitopes and to subdomain 1 of SARS-CoV-2. , 4 days ago. , Article ... Identification of epitopes on respiratory syncytial virus proteins by competitive binding immunoassay. , 22 hours ...
Chemical sensing in development and function of intestinal lymphocytes. Cervantes-Barragan, L. & Colonna, M., Feb 2018, In: ...
T-Lymphocytes/immunology*. Find related publications in this database (Keywords). Phl p 5 Epitope mapping Tetramers BALB/c ... T cell epitopes of the timothy grass pollen allergen Phl p 5 of mice and men and the detection of allergen-specific T cells ... Knowledge of allergen-specific T cell epitopes is a prerequisite not only for therapeutic approaches but also for elucidating ...
... cytotoxic T lymphocytes (CTL). In a phase I clinical trial of survivin-2B80-88 vaccination for metastatic urothelial cancer ( ... Y. Hirohashi, T. Torigoe, A. Maeda et al., "An HLA-A24-restricted cytotoxic T lymphocyte epitope of a tumor-associated protein ... Immunization with peptides derived from cancer-specific antigen induces antitumor cytotoxic T lymphocytes (CTLs) [7-9]. A large ... cytotoxic T lymphocytes (CTL). In a phase I clinical trial of survivin-2B80-88 vaccination for metastatic urothelial cancer ( ...
Evolution of epitopes on human and nonhuman primate lymphocyte cell surface antigens. E. Clark et al. 0 Absolute Lymphocyte ...
  • Incubation of spleen cells from mice having rejected a Moloney sarcoma virus (MSV)‐induced tumor with syngeneic irradiated lymphoma or sarcoma cells bearing MSV‐associated antigens in secondary mixed leukocyte‐tumor cell cultures (MLTC) resulted in the generation of highly active cytolytic T lymphocytes (CTL) specifically directed against syngeneic target cells bearing MSV‐associated antigens. (
  • Evolution of epitopes on human and nonhuman primate lymphocyte cell surface antigens. (
  • Epitopes to which antigens most readily respond should be chosen to make the vaccine because this is what antibodies , B lymphocytes, and T lymphocytes will respond to. (
  • Derived, Modified Epitope Peptide, Using Dendritic Cells as a Peptide Delivery System. (
  • Induction of Cytotoxic T Lymphocytes by Immunization with Dengue Virus - Derived, Modified Epitope Peptide, Using Dendritic Cells as a Peptide Delivery System. (
  • A single 9-amino acid peptide of the defined murine cytotoxic T lymphocyte (CTL) epitope (named peptide-1), which corresponds to the amino acid residues 298-306 (GYISTRVEM) of NS3 of dengue virus serotypes DEN-2 and 4, was examined for induction of specific CTLs. (
  • These results indicate that immunization with dengue virus-derived CTL epitope peptide induces specific CTLs, and that DC can be used as a vehicle for the modified epitope peptide. (
  • It is important to analyse peptide-1 and 96.2% for the peptide-2 by CTL responses elicited by a single epitope in reverse phase HPLC. (
  • The results suggest that the quality of the response (polyfunctionality) could be associated with the binding affinity of the peptide to the HLA molecule, and the functional profile of specific CD8 + T-cells to mutated epitopes in individuals under cART is maintained. (
  • While the theoretical diversity of T cell receptor (TCR) sequences is vast, the antigen-specific TCR repertoire is restricted by its peptide epitope and the presenting major histocompatibility complex (pMHC). (
  • We previously identified a human leukocyte antigen (HLA)-A24-restricted antigenic peptide, survivin-2B80-88, a member of the inhibitor of apoptosis protein family, recognized by CD8+cytotoxic T lymphocytes (CTL). (
  • Flow Pharma, Inc. is a biotechnology company in the San Francisco Bay Area developing fully synthetic cytotoxic T lymphocyte (CTL)stimulating peptide vaccines for Marburg virus. (
  • Novel Nested Peptide Epitopes Recognized by CD4+ T Cells Induced by HIV-1 Conserved-Region Vaccines. (
  • A synthetic peptide derived from the EA-D molecule which contains an epitope reactive with immune human sera from patients with IM and other disease states has also been described (Fox, et al. (
  • Interestingly, Mamu-B*08-restricted SIV-derived epitopes appeared to match the peptide binding profile for HLA-B*2705 in humans. (
  • Detailed knowledge of the Mamu-B*08 peptide-binding motif enabled us to identify six additional novel Mamu-B*08-restricted SIV-specific CD8(+) T cell immune responses directed against epitopes in Gag, Vpr, and Env. (
  • To understand the CD8+ T cell immunity related to viral protection and disease severity in COVID-19, we evaluated the complete SARS-CoV-2 genome (3141 MHC-I binding peptides) to identify immunogenic T cell epitopes, and determine the level of CD8+ T cell involvement using DNA-barcoded peptide-major histocompatibility complex (pMHC) multimers. (
  • Since this defect could be conquer by administration of huge dosages of IVIG generally in most KD individuals, our results claim that the administration of Fc-derived peptide epitopes could be a practical therapeutic method of increase Fc-specific nTreg and stop CAA. (
  • In view of the most recent information that CD-1 MAB recognize at least three different early T-cell differentiation molecules, our results indicate that there are three or more distinct epitopes on the 'gp49'(HTA-1/CD-1a) molecule, two on the 'gp45'(HTA-3/CD-1b) molecule and one on 'gp43'(HTA-2/CD-1c). (
  • Researchers at the National Cancer Institute's Experimental Transplantation and Immunology Branch (NCI ETIB) developed a T Cell receptor that specifically targets the Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1) 52-60 epitope that is highly expressed by several common and aggressive epithelial tumor types. (
  • The kit is optimized for high yield of tumor cells and tumor-infiltrating lymphocytes, while preserving important cell surface epitopes. (
  • However, the strong immune pressure of CD8 + T-cells causes the selection of viral variants with mutations in immunodominant epitopes. (
  • This activity is required to generate signal sequence-derived human lymphocyte antigen-E epitopes that are recognized by the immune system, and to process hepatitis C virus core protein. (
  • Epitopes are a component of the antigen that are recognized by the immune system and determine whether the cellular or the humoral arm of the immune system shall be activated against that particular antigen. (
  • The presence of IgG- α 1 PI immune complexes correlated with decreased CD4 + lymphocytes in HIV-1 individuals, and α1PI augmentation quadrupled the number of immunocompetent CD4 + lymphocytes with no untoward effects. (
  • We performed a survey ( 4 ) for known human immune epitopes present in the various proteins of seasonal influenza A virus strains and known to be efficient in stimulating lymphocytes. (
  • Human immunodeficiency virus (HIV)-1 amino acid sequence polymorphisms associated with expression of specific human histocompatibility leukocyte antigen (HLA) class I alleles suggest sites of cytotoxic T lymphocyte (CTL)-mediated selection pressure and immune escape. (
  • If an escape variant reaches fixation in the population, the epitope will be lost as a potential target to the immune system. (
  • Potential targets for immune checkpoint inhibition are lymphocyte-activation gene 3 (LAG3) and its ligands. (
  • The cellular response is mainly a lymphocyte-mediated reaction, whereas the humoral response includes production of antibodies against the antigen by the plasma cells. (
  • Immunoglobulins (Igs), the term is sometimes used interchangeably with "antibodies," are glycoprotein molecules produced by B lymphocytes and plasma cells in response to an immunogen or after recognition of specific epitopes on the antigen. (
  • Antibodies can be found on the surface of lymphocytes as an integral part of the cell membrane protein or can be freely circulating in the blood or be part of one of the body's gland secretion. (
  • Human monoclonal antibodies that recognize conserved epitopes in the core-lipid A region of lipopolysaccharides. (
  • Epstein-Barr virus (EBV)-transformed human B lymphocytes were fused with a murine-human heteromyeloma to produce stable hybrid cell lines that secreted human monoclonal antibodies (mAbs) of the IgM class that recognized conserved epitopes in the core-lipid A region of lipopolysaccharides (LPS). (
  • These findings confirm the presence of highly conserved epitopes in the core-lipid A complex and prove the existence of human B cell clones with the potential for secreting high avidity IgM antibodies that react with these widely shared determinants. (
  • The antibodies that are formed will attach to these epitopes if a person is infected. (
  • This lack of detection of MN or HI antibodies is probably because most of these epitopes may not elicit MN/HI detectable antibodies, or these epitopes may be present in earlier seasonal influenza strains but not present in the current trivalent, inactivated influenza vaccine. (
  • Even though many do not contribute to neutralizing antibodies, these MHC class II antigen-restricted epitopes may initiate the Th1 response, including activation of infected macrophages and antiviral cytokine production, and help host defenses as well. (
  • The development of CD8 + T-cell-based vaccine against HIV-1 has focused on searching for immunodominant epitopes. (
  • COVID-19 patients showed strong T cell responses, with up to 25% of all CD8+ lymphocytes specific to SARS-CoV-2-derived immunodominant epitopes, derived from ORF1 (open reading frame 1), ORF3, and Nucleocapsid (N) protein. (
  • CLL is now viewed as two related entities, both originating from antigen-stimulated mature B lymphocytes, which either avoid death through the intercession of external signals or die by apoptosis, only to be replenished by proliferating precursor cells. (
  • Tafasitamab is a humanized Fc-modified cytolytic CD19-directed monoclonal antibody that binds to the CD19 antigen expressed on the surface of pre-B and mature B lymphocytes and on several B-cell malignancies. (
  • Induction of Cytotoxic T Lymphocytes by Immunization with Dengue Virus potential risk that the immunogen may be the Animal Facility of Kinki University School pathogenic. (
  • Journal Article] Identification of EphB6 variant-derived epitope peptides recognized by cytotoxic T-lymphocytes from HLA-A24^+ malignant glioma patients. (
  • Journal Article] EphB6 variant-derived peptides with the ability to induce glioma-reactive cytotoxic T lymphocytes in HLA-A2+ glioma patients. (
  • Immunization with peptides derived from cancer-specific antigen induces antitumor cytotoxic T lymphocytes (CTLs) [ 7 - 9 ]. (
  • METHODS: The linear epitopes of P120 and P80 were predicted by the Kolaskar and Tongaonkar Antigenicity method. (
  • have CTL epitope expressed in host cells by infection with live viruses, or by Major histocompatibility complex (MHC) administration of an expression plasmid class I - restricted, CD8+ cytotoxic T vector (i.e. (
  • The other is essential role in the recovery from viral immunization with a defined CTL epitope infection by lysing virus-infected cells [1] . (
  • One mechanism reported to regulate the proliferative capacity of activated lymphocytes is mediated by the effect of telomerase in maintaining the length of telomeres in proliferating cells. (
  • This HLA B7-restricted epitope in nucleoprotein (NP) was detectable in four healthy, B7-positive adult subjects using B7-RSV-NP tetrameric complexes to stain CD8(+) T cells. (
  • and when sequential exposure intervals are long, consistent with ongoing selection and expansion of lymphocyte clones that have increasing antibody avidity at key cross-reactive epitopes ( 7 - 10 ) and possibly with epitope competition between naïve and antigen-specific B cells ( 8 ). (
  • In the present work, peripheral blood mononuclear cells from 12 HIV-1 + HLA-A*02:01 + individuals were stimulated with the mutated and wild-type peptides derived from the GC9 and SL9 epitopes. (
  • T cell epitopes of the timothy grass pollen allergen Phl p 5 of mice and men and the detection of allergen-specific T cells using Class II Ultimers. (
  • Lymphocytes from an HLA-B7 DW2 homozygous multiparous woman, J.H., failed to respond in the mixed lymphocyte reaction to lymphocytes from her DW1 homozygous husband, W.H., and certain other homozygous typing cells. (
  • However, a combined regime whereby the animals were first primed with the DNA vaccine and then boosted with MVA was the most potent protocol for the induction of both interferon-gamma-producing and cytolytic T cells against two CTL epitopes simultaneously. (
  • CD8+ T cells from SIV elite controller macaques recognize Mamu-B*08-bound epitopes and select for widespread viral variation. (
  • Indeed, we found evidence for selection pressure mediated by Mamu-B*08-restricted CD8+ T cells in all of the newly identified epitopes in a cohort of chronically infected macaques. (
  • The development of skin sensitization is associated with, and requires, the activation and clonal expansion of allergen responsive T lymphocytes and it is these cells that orchestrate the cutaneous allergic reaction. (
  • Spleen cells from cured mice developed CTL activity and produced IFN-γ in response to stimulation by the AH1 epitope of the gp70env Ag of TS/A-pc. (
  • IL-21R expression on CD25 - lymphocytes suggested that IL-21 could be more effective in mice depleted of CD25 + cells. (
  • We previously demonstrated the adaptation of circulating strains of HIV-1 to the HLA-A*02 molecule by identifying mutations under positive selection located in GC9 and SL9 epitopes derived from the Gag protein. (
  • An epitope is one specific region of a protein molecule. (
  • METHODS AND FINDINGS:Here we show that three ECs in that study made at least seven robust CD8+ T cell responses directed against novel epitopes in Vif, Rev, and Nef restricted by the MHC class I molecule Mamu-B*08. (
  • Tumor necrosis factor superfamily 14 (TNFSF14) (LIGHT) is an interesting costimulatory molecule associated with T lymphocyte activation, and it mainly exerts its biological effects by binding to its receptors herpesvirus invasion mediator (HVEM) and lymphotoxin-ß receptor. (
  • RESULTS: From 26 primary predicted epitopes, 15 were recognized as specific peptides and further evaluation led to selection of 8 for the construction of a chimeric protein. (
  • The chimeric protein designed based on consensus predicted epitopes holds promise for the diagnosis of M. hominis infection. (
  • This protein participates in a wide variety of cellular functions including lymphocyte activation, recirculation and homing, hematopoiesis, and tumor metastasis. (
  • First a good target protein or epitope needs to be found for the pathogen of interest. (
  • We found that multiple major histocompatibility complex (MHC)-restricted epitopes are conserved in nucleoprotein (NP) and matrix protein (MP), and even a few in the more variable hemagglutinin (HA) protein, in A/California/04/2009, A/Texas/04/2009, and A/New York/18/2009. (
  • In addition, ≈15 completely conserved epitopes are in the M protein of pandemic (H1N1) 2009 virus (data not shown). (
  • We now demonstrate that one or more genes encoded within the MHC selectively censor the ability of H-2(b) mice to mount this conformation-dependent autoantibody response, while leaving T and B cell responses to linear MOG(Igd) epitopes intact. (
  • DNA vaccine) in which the lymphocytes (CTLs) are known to play an epitope gene is incorporated. (
  • The FlowVax vaccine platform allows us to create dry powder formulations of biodegradablemicrospheres and TLR adjuvants incorporating class I and class II T cell epitopes. (
  • Tedopi is a neo-epitope-based vaccine that activates T lymphocytes, which researchers hope will optimize the checkpoint inhibitor or chemotherapy in patients who have become resistant. (
  • Altogether 59 BNT162b2 vaccine-derived immunogenic epitopes were identified, of which 23 established long-term CD8+ T cell memory response with a strong immunodominance for NYNYLYRLF (HLA-A24:02) and YLQPRTFLL (HLA-A02:01) epitopes. (
  • Later studies by many investigators showed original antigenic sin to be a general phenomenon associated with numerous related/sequentially infecting virus strains that contain multiple external epitopes of varying cross-specificity (i.e., ability to elicit cross-reactive antibody), including antigenically drifting viruses such as influenza A, and the more stable flaviviruses, which circulate concurrently as multiple distinct viruses, virus serotypes, and virus strains ( 7 , 8 ). (
  • An epitope may represent a linear amino acid sequence or antigenic tertiary structure. (
  • Antigenic specificity of the cytolytic T lymphocyte (CTL) response to murine sarcoma virus‐induced tumors. (
  • Carbohydrate groups in the O-side chain and core oligosaccharide of isolated, smooth LPS restricted antibody access to antigenic sites on lipid A. Yet, one lipid A-reactive mAb recognized its epitope on the surfaces of a variety of intact bacteria. (
  • Knowledge of allergen-specific T cell epitopes is a prerequisite not only for therapeutic approaches but also for elucidating immunological mechanisms of type I allergy. (
  • In this study, we used circulating lymphocytes isolated from human blood and found that rotenone (50-250microM, 12-18h) caused apoptosis (phosphatidylserine externalization, caspase 3/7 activation), reactive oxygen species production (superoxide, H2O2), mitochondrial dysfunction (inactivation of complex I, decrease of mitochondria membrane potential, depletion of ATP) and activation of peroxidase activity of mitochondria. (
  • For MHC class I antigen-restricted epitopes essential for CD8+ T cell activation and CMI, HA of pandemic (H1N1) 2009 virus contains HLA-A*0201-restricted GLFGAIAGFI ( 6 ), which is present also in the HA of A/New Caledonia/20/1999 (H1N1) and A/Solomon Islands/3/2006 (H1N1) viruses. (
  • The 581 antibody recognizes the class III group epitope which is resistant to sialidase/glycolyprotease and chymopapain treatment. (
  • For MHC class II antigen-restricted epitopes essential for antibody and Th1 responses, HA of pandemic (H1N1) 2009 virus contains HLA-DRA*0101/DRB1 *0101-restricted SVIEKMNTQFTAV ( 5 ), as well as HLA-DRA*0101/DRB1*0401-restricted EKMNTQFTAVGKE, TGLRNIPSIQSRG, and ELLVLLENERTLDY ( 5 ), and HLA-DRB5*0101-restricted DYEELREQLSSVSSFERFE ( 5 ) epitopes. (
  • All seven regions encoding Mamu-B*08-restricted CD8+ T cell epitopes also exhibit amino acid replacements typically seen only in the presence of Mamu-B*08, suggesting that the variation we observe is indeed selected by CD8+ T cell responses. (
  • Identification of Kaposi's sarcoma-associated herpesvirus (KSHV)-specific cytotoxic T-lymphocyte epitopes and evaluation of reconstitution of KSHV-specific responses in human immunodeficiency virus type 1-Infected patients receiving highly active antiretroviral therapy. (
  • After excluding non-specific epitopes, the remaining peptides were further analyzed by the BepiPred Linear Epitope Prediction method. (
  • CONCLUSIONS: There are several bioinformatics tools for prediction of B-cell epitopes using different algorithms. (
  • The prediction of epitope recognition by T-cell receptors (TCRs) has seen many advancements in recent years, with several methods now available that can predict recognition for a specific set of epitopes. (
  • These antigen-restricted epitopes were present in globally-distributed seasonal H1N1 viruses, including classical A/New Caledonia/20/1999 (H1N1) and A/Solomon Islands/3/2006 (H1N1). (
  • More MHC class I antigen-restricted epitopes in NP and MP of seasonal epidemic influenza viruses (H1N1) and (H3N2) are conserved in pandemic (H1N1) virus. (
  • Because of a high rate of sequence polymorphism, it is necessary to recognize and select conserved epitopes from bacterial surface proteins. (
  • This study was conducted to predict and evaluate appropriate epitopes of two membrane proteins, P120 and P80, by bioinformatics tools. (
  • The first human RSV-specific cytotoxic T-lymphocyte epitope to be defined is described. (
  • Chimpanzee α 1 PI differs from human α 1 PI by a single amino acid which lies within the 3F5-binding epitope. (
  • Unlike human α 1 PI, neither chimpanzee nor macaque α 1 PI bound to 3F5, nor was α 1 PI depleted following HIV-1 challenge, consistent with the normal CD4 + lymphocyte numbers of HIV-1 infected chimpanzees. (
  • A suppressor T cell in the human mixed lymphocyte reaction. (
  • Notably, molecular species of oxygenated CL formed in human lymphocytes were similar to those formed in cyt c driven reaction in the presence of H2O2 - in line with the known participation of cytochrome as a catalyst of CL peroxidation during apoptosis. (
  • This approach is based on the pairwise combination of physicochemical properties of the individual amino acids in the CDR3 and epitope sequences, which provides a convolutional neural network with the combined representation of both sequences. (
  • Autoantibodies directed against conformation-dependent epitopes of the extracellular domain of the myelin oligodendrocyte glycoprotein (MOG(Igd)) play a major role in the immunopathogenesis of demyelination in experimental autoimmune encephalomyelitis. (
  • According to the differential sensitivity to enzymatic cleavage, four groups of epitopes of CD34 have been described. (
  • Using the combination of lipidomics and oxidative epitope-targeted enzymatic digestion of oxidized tetralinoleoyl-CL we found that its oxygenated LA species were represented by hydroxy- and hydroperoxy-derivatives. (
  • In addition we were able to detect oxygenated molecular species of tetra-linoleyl CL, a major CL molecular species in lymphocytes. (
  • Lastly, we highlight various challenges that are specific to TCR-epitope data and that can adversely affect model performance. (
  • Despite the initial high number of deaths among patients in Mexico and among patients with specific preexisting conditions, pandemic (H1N1) 2009 virus in general has caused mild symptoms, and the overall death rate remains around 0.45% ( ). (
  • The compound is a chimeric mAb targeting an epitope on the CD20 antigen found on B lymphocytes. (
  • The TCR may be used in an adoptive cell therapy approach utilizing genetically engineered lymphocytes to treat HPV-positive malignancies. (
  • This antibody's epitope is resistant to digestion by trypsin and chymotrypsin. (
  • The current studies, focusing on two examples of "negatively associated" or apparently preserved epitopes, suggest an explanation for this phenomenon: negative associations can arise as a result of positive selection of an escape mutation, which is stable on transmission and therefore accumulates in the population to the point at which it defines the consensus sequence. (
  • First, we examine appropriate validation strategies to accurately assess the generalization performance of generic TCR-epitope recognition models when applied to both seen and unseen epitopes. (
  • Our results indicate that while extrapolation to unseen epitopes remains a difficult challenge, ImRex makes this feasible for a subset of epitopes that are not too dissimilar from the training data. (