Antigen Presentation: 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)Antigens: Substances that are recognized by the immune system and induce an immune reaction.Histocompatibility Antigens Class II: 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.Antigens, Bacterial: Substances elaborated by bacteria that have antigenic activity.Antigen-Presenting Cells: A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.Antigens, Neoplasm: Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.Antigens, Surface: 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.Antigens, Viral: Substances elaborated by viruses that have antigenic activity.Dendritic Cells: 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).Histocompatibility Antigens Class I: 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.T-Lymphocytes: 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.Lymphocyte Activation: 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.HLA-DR Antigens: 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.Antigens, CD: 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.H-2 Antigens: The major group of transplantation antigens in the mouse.HLA-D Antigens: Human immune-response or Class II antigens found mainly, but not exclusively, on B-lymphocytes and produced from genes of the HLA-D locus. They are extremely polymorphic families of glycopeptides, each consisting of two chains, alpha and beta. This group of antigens includes the -DR, -DQ and -DP designations, of which HLA-DR is most studied; some of these glycoproteins are associated with certain diseases, possibly of immune etiology.Antigens, CD1: Glycoproteins expressed on cortical thymocytes and on some dendritic cells and B-cells. Their structure is similar to that of MHC Class I and their function has been postulated as similar also. CD1 antigens are highly specific markers for human LANGERHANS CELLS.Mice, Inbred C57BLMice, Inbred BALB CHLA Antigens: 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.Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily.Antigens, Protozoan: Any part or derivative of any protozoan that elicits immunity; malaria (Plasmodium) and trypanosome antigens are presently the most frequently encountered.Epitopes: Sites on an antigen that interact with specific antibodies.B-Lymphocytes: 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.T-Lymphocytes, Cytotoxic: 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.CD8-Positive T-Lymphocytes: 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.Antigens, Polyomavirus Transforming: Polyomavirus antigens which cause infection and cellular transformation. The large T antigen is necessary for the initiation of viral DNA synthesis, repression of transcription of the early region and is responsible in conjunction with the middle T antigen for the transformation of primary cells. Small T antigen is necessary for the completion of the productive infection cycle.Receptors, Antigen, T-Cell: 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.CD4-Positive T-Lymphocytes: 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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Histocompatibility Antigens: 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.Receptors, Antigen, B-Cell: 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.Major Histocompatibility Complex: 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.Antigens, Fungal: Substances of fungal origin that have antigenic activity.Hybridomas: 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.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Antigens, CD1d: A major histocompatibily complex class I-like protein that plays a unique role in the presentation of lipid ANTIGENS to NATURAL KILLER T-CELLS.Antigens, Differentiation, B-Lymphocyte: Membrane antigens associated with maturation stages of B-lymphocytes, often expressed in tumors of B-cell origin.Cells, Cultured: 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.Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.Genes, MHC Class II: Genetic loci in the vertebrate major histocompatibility complex that encode polymorphic products which control the immune response to specific antigens. The genes are found in the HLA-D region in humans and in the I region in mice.Flow Cytometry: 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.Interferon-gamma: 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.Molecular Sequence Data: 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.Antigens, Helminth: Any part or derivative of a helminth that elicits an immune reaction. The most commonly seen helminth antigens are those of the schistosomes.Monitoring, Physiologic: The continuous measurement of physiological processes, blood pressure, heart rate, renal output, reflexes, respiration, etc., in a patient or experimental animal; includes pharmacologic monitoring, the measurement of administered drugs or their metabolites in the blood, tissues, or urine.Cross-Priming: Class I-restricted activation of CD8-POSITIVE LYMPHOCYTES resulting from ANTIGEN PRESENTATION of exogenous ANTIGENS (cross-presentation). This is in contrast to normal activation of these lymphocytes (direct-priming) which results from presentation of endogenous antigens.Antigens, CD86: A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CD28 ANTIGEN with high specificity and to CTLA-4 ANTIGEN with low specificity. The interaction of CD86 with CD28 ANTIGEN provides a stimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.Antigens, CD8: 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.Transcription Factor Brn-3B: A POU domain factor that represses GENETIC TRANSCRIPTION of GENES encoding NEUROFILAMENT PROTEINS, alpha internexin, and SYNAPTOSOMAL-ASSOCIATED PROTEIN 25.Amino Acid Sequence: 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.Spleen: An encapsulated lymphatic organ through which venous blood filters.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Carcinoembryonic Antigen: A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the response to colon cancer treatment.Antigens, Viral, Tumor: Those proteins recognized by antibodies from serum of animals bearing tumors induced by viruses; these proteins are presumably coded for by the nucleic acids of the same viruses that caused the neoplastic transformation.Antigens, CD40: A member of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. It is found on mature B-LYMPHOCYTES and some EPITHELIAL CELLS, lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations of the gene for CD40 antigen result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.Macrophages: 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.)HLA-A Antigens: 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.Immune Tolerance: 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.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Enzyme-Linked Immunosorbent Assay: 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.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Proteasome Endopeptidase Complex: A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.LebanonImmunization: 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).Proliferating Cell Nuclear Antigen: Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.Lymph Nodes: They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.Antibody Formation: The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.Cytotoxicity, Immunologic: 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.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Epitopes, T-Lymphocyte: 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.Receptor, EphA5: An eph family receptor found primarily in differentiated neuronal tissues. Several isoforms of EphA5 receptor occur due to multiple alternative RNA splicing. The protein is prominently expressed in the NEURONS of the LIMBIC SYSTEM during development and throughout adult life, suggesting its role in the plasticity of limbic structure and function.Prostate-Specific Antigen: A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer.O Antigens: The lipopolysaccharide-protein somatic antigens, usually from gram-negative bacteria, important in the serological classification of enteric bacilli. The O-specific chains determine the specificity of the O antigens of a given serotype. O antigens are the immunodominant part of the lipopolysaccharide molecule in the intact bacterial cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Autoantigens: Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.Cross Reactions: Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.Antigens, CD4: 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.Cysteine Endopeptidases: ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.Cytokines: 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.HLA-B Antigens: 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.Antigens, CD3: 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).Hepatitis B Surface Antigens: Those hepatitis B antigens found on the surface of the Dane particle and on the 20 nm spherical and tubular particles. Several subspecificities of the surface antigen are known. These were formerly called the Australia antigen.Monocytes: 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.ATP-Binding Cassette Transporters: A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.Immunity, Cellular: 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.Antigens, CD15: A trisaccharide antigen expressed on glycolipids and many cell-surface glycoproteins. In the blood the antigen is found on the surface of NEUTROPHILS; EOSINOPHILS; and MONOCYTES. In addition, CD15 antigen is a stage-specific embryonic antigen.HLA-DQ Antigens: A group of the D-related HLA antigens found to differ from the DR antigens in genetic locus and therefore inheritance. These antigens are polymorphic glycoproteins comprising alpha and beta chains and are found on lymphoid and other cells, often associated with certain diseases.Fluorescent Antibody Technique: 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.Clone Cells: 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)Antigens, Tumor-Associated, Carbohydrate: Carbohydrate antigens expressed by malignant tissue. They are useful as tumor markers and are measured in the serum by means of a radioimmunoassay employing monoclonal antibodies.Antibody Specificity: 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.Models, Immunological: 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.Mice, Inbred C3HMice, Knockout: 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.Dose-Response Relationship, Immunologic: A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Mice, Inbred CBAHLA-B27 Antigen: A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*27 allele family.Adjuvants, Immunologic: 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.Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.Endosomes: Cytoplasmic vesicles formed when COATED VESICLES shed their CLATHRIN coat. Endosomes internalize macromolecules bound by receptors on the cell surface.Antigens, CD11c: An integrin alpha subunit of approximately 150-kDa molecular weight. It is expressed at high levels on monocytes and combines with CD18 ANTIGEN to form the cell surface receptor INTEGRIN ALPHAXBETA2. The subunit contains a conserved I-domain which is characteristic of several of alpha integrins.HLA-B7 Antigen: A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*07 allele family.MART-1 Antigen: A melanosome-specific protein that plays a role in the expression, stability, trafficking, and processing of GP100 MELANOMA ANTIGEN, which is critical to the formation of Stage II MELANOSOMES. The protein is used as an antigen marker for MELANOMA cells.Blood Group Antigens: Sets of cell surface antigens located on BLOOD CELLS. They are usually membrane GLYCOPROTEINS or GLYCOLIPIDS that are antigenically distinguished by their carbohydrate moieties.H-Y Antigen: A sex-specific cell surface antigen produced by the sex-determining gene of the Y chromosome in mammals. It causes syngeneic grafts from males to females to be rejected and interacts with somatic elements of the embryologic undifferentiated gonad to produce testicular organogenesis.Immune Evasion: Methods used by pathogenic organisms to evade a host's immune system.Immunologic Memory: 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.Immune Sera: 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.Tumor Cells, Cultured: 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.Hypersensitivity, Delayed: An increased reactivity to specific antigens mediated not by antibodies but by cells.Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.Cavernous Sinus Thrombosis: Formation or presence of a blood clot (THROMBUS) in the CAVERNOUS SINUS of the brain. Infections of the paranasal sinuses and adjacent structures, CRANIOCEREBRAL TRAUMA, and THROMBOPHILIA are associated conditions. Clinical manifestations include dysfunction of cranial nerves III, IV, V, and VI, marked periorbital swelling, chemosis, fever, and visual loss. (From Adams et al., Principles of Neurology, 6th ed, p711)Antigens, Differentiation: 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.Epstein-Barr Virus Nuclear Antigens: Nuclear antigens encoded by VIRAL GENES found in HUMAN HERPESVIRUS 4. At least six nuclear antigens have been identified.T-Lymphocytes, Helper-Inducer: 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.Immunodominant Epitopes: Subunits of the antigenic determinant that are most easily recognized by the immune system and thus most influence the specificity of the induced antibody.Cancer Vaccines: 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.Phagocytosis: The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).Antigens, CD79: A component of the B-cell antigen receptor that is involved in B-cell antigen receptor heavy chain transport to the PLASMA MEMBRANE. It is expressed almost exclusively in B-LYMPHOCYTES and serves as a useful marker for B-cell NEOPLASMS.Langerhans Cells: Recirculating, dendritic, antigen-presenting cells containing characteristic racket-shaped granules (Birbeck granules). They are found principally in the stratum spinosum of the EPIDERMIS and are rich in Class II MAJOR HISTOCOMPATIBILITY COMPLEX molecules. Langerhans cells were the first dendritic cell to be described and have been a model of study for other dendritic cells (DCs), especially other migrating DCs such as dermal DCs and INTERSTITIAL DENDRITIC CELLS.HLA-DR1 Antigen: An HLA-DR antigen associated with HLA-DRB1 CHAINS that are encoded by DRB1*01 alleles.Antibodies: 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).Alum Compounds: Aluminum metal sulfate compounds used medically as astringents and for many industrial purposes. They are used in veterinary medicine for the treatment of ulcerative stomatitis, leukorrhea, conjunctivitis, pharyngitis, metritis, and minor wounds.Antigens, CD45: 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.HLA-DR3 Antigen: An HLA-DR antigen which is associated with HLA-DRB1 CHAINS encoded by DRB1*03 alleles.Transfection: 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.Receptors, Antigen: Molecules on the surface of B- and T-lymphocytes that recognize and combine with specific antigens.Viral Proteins: Proteins found in any species of virus.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Immunophenotyping: 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.Hepatitis B Antigens: Antigens of the virion of the HEPATITIS B VIRUS or the Dane particle, its surface (HEPATITIS B SURFACE ANTIGENS), core (HEPATITIS B CORE ANTIGENS), and other associated antigens, including the HEPATITIS B E ANTIGENS.Rhabditida: An order of nematodes of the subclass SECERNENTEA. Its organisms are characterized by an annulated or smooth cuticle and the absence of caudal glands.Antigen-Antibody Reactions: The processes triggered by interactions of ANTIBODIES with their ANTIGENS.HLA-DR7 Antigen: A HLA-DR antigen that is associated with HLA-DRB1 CHAINS encoded by DRB1*07 alleles.Antibodies, Bacterial: Immunoglobulins produced in a response to BACTERIAL ANTIGENS.Recombinant Fusion Proteins: 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.Receptors, IgG: Specific molecular sites on the surface of various cells, including B-lymphocytes and macrophages, that combine with IMMUNOGLOBULIN Gs. Three subclasses exist: Fc gamma RI (the CD64 antigen, a low affinity receptor), Fc gamma RII (the CD32 antigen, a high affinity receptor), and Fc gamma RIII (the CD16 antigen, a low affinity receptor).Pinocytosis: The engulfing of liquids by cells by a process of invagination and closure of the cell membrane to form fluid-filled vacuoles.beta 2-Microglobulin: An 11-kDa protein associated with the outer membrane of many cells including lymphocytes. It is the small subunit of the MHC class I molecule. Association with beta 2-microglobulin is generally required for the transport of class I heavy chains from the endoplasmic reticulum to the cell surface. Beta 2-microglobulin is present in small amounts in serum, csf, and urine of normal people, and to a much greater degree in the urine and plasma of patients with tubular proteinemia, renal failure, or kidney transplants.T-Lymphocyte Subsets: A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Muramidase: A basic enzyme that is present in saliva, tears, egg white, and many animal fluids. It functions as an antibacterial agent. The enzyme catalyzes the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrin. EC 3.2.1.17.Lectins, C-Type: A class of animal lectins that bind to carbohydrate in a calcium-dependent manner. They share a common carbohydrate-binding domain that is structurally distinct from other classes of lectins.Protein Binding: 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.HemocyaninPotassium Radioisotopes: Unstable isotopes of potassium that decay or disintegrate emitting radiation. K atoms with atomic weights 37, 38, 40, and 42-45 are radioactive potassium isotopes.Lymphocytes: 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.Signal Transduction: 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.Interleukin-2: A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.Vaccines, DNA: 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.Adoptive Transfer: 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).Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Bone Marrow Cells: Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.Gene Expression Regulation: 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.Immunoglobulins: 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.Immunoglobulin M: 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.CD40 Ligand: A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Cathepsins: A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissues. They function optimally within an acidic pH range. The cathepsins occur as a variety of enzyme subtypes including SERINE PROTEASES; ASPARTIC PROTEINASES; and CYSTEINE PROTEASES.Catalogs, UnionReceptors, Antigen, T-Cell, alpha-beta: 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.Genetic Vectors: 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.Dry Ice: A solid form of carbon dioxide used as a refrigerant.Vaccinia virus: 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.Phagosomes: Membrane-bound cytoplasmic vesicles formed by invagination of phagocytized material. They fuse with lysosomes to form phagolysosomes in which the hydrolytic enzymes of the lysosome digest the phagocytized material.CTLA-4 Antigen: An inhibitory T CELL receptor that is closely related to CD28 ANTIGEN. It has specificity for CD80 ANTIGEN and CD86 ANTIGEN and acts as a negative regulator of peripheral T cell function. CTLA-4 antigen is believed to play role in inducing PERIPHERAL TOLERANCE.RNA, Messenger: 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.Porosity: Condition of having pores or open spaces. This often refers to bones, bone implants, or bone cements, but can refer to the porous state of any solid substance.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Lymphocyte Cooperation: T-cell enhancement of the B-cell response to thymic-dependent antigens.Isoantigens: Antigens that exist in alternative (allelic) forms in a single species. When an isoantigen is encountered by species members who lack it, an immune response is induced. Typical isoantigens are the BLOOD GROUP ANTIGENS.HIV Antigens: 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.Antibodies, Viral: Immunoglobulins produced in response to VIRAL ANTIGENS.Breech Presentation: A malpresentation of the FETUS at near term or during OBSTETRIC LABOR with the fetal cephalic pole in the fundus of the UTERUS. There are three types of breech: the complete breech with flexed hips and knees; the incomplete breech with one or both hips partially or fully extended; the frank breech with flexed hips and extended knees.Immunity: Nonsusceptibility to the invasive or pathogenic effects of foreign microorganisms or to the toxic effect of antigenic substances.Antigens, CD28: 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.Histocompatibility Antigen H-2D: A component of the murine major histocompatibility complex class I family. It contains one Ig-like C1-type domain and functions in processing and presentation of exogenous peptide antigens to the immune system.Th1 Cells: 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.Androgens: Compounds that interact with ANDROGEN RECEPTORS in target tissues to bring about the effects similar to those of TESTOSTERONE. Depending on the target tissues, androgenic effects can be on SEX DIFFERENTIATION; male reproductive organs, SPERMATOGENESIS; secondary male SEX CHARACTERISTICS; LIBIDO; development of muscle mass, strength, and power.Muromegalovirus: A genus of the family HERPESVIRIDAE, subfamily BETAHERPESVIRINAE, causing infection involving several organs in mice and rats. Murid herpesvirus is the type species.Delftia acidovorans: A species of gram-negative rod-shaped bacteria found ubiquitously and formerly called Comamonas acidovorans and Pseudomonas acidovorans. It is the type species of the genus DELFTIA.HLA-DR2 Antigen: A broad specificity HLA-DR antigen that is associated with HLA-DRB1 CHAINS encoded by DRB1*01:15 and DRB1*01:16 alleles.Minor Histocompatibility Antigens: Allelic alloantigens often responsible for weak graft rejection in cases when (major) histocompatibility has been established by standard tests. In the mouse they are coded by more than 500 genes at up to 30 minor histocompatibility loci. The most well-known minor histocompatibility antigen in mammals is the H-Y antigen.Cell Line, Transformed: 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.Vaccines, Synthetic: 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.HLA-C Antigens: Class I human histocompatibility (HLA) antigens encoded by a small cluster of structural genes at the C locus on chromosome 6. They have significantly lower immunogenicity than the HLA-A and -B determinants and are therefore of minor importance in donor/recipient crossmatching. Their primary role is their high-risk association with certain disease manifestations (e.g., spondylarthritis, psoriasis, multiple myeloma).Immunoenzyme Techniques: Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.Cytomegalovirus: A genus of the family HERPESVIRIDAE, subfamily BETAHERPESVIRINAE, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS.Cell Communication: 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.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Aminopeptidases: A subclass of EXOPEPTIDASES that act on the free N terminus end of a polypeptide liberating a single amino acid residue. EC 3.4.11.Listeria monocytogenes: A species of gram-positive, rod-shaped bacteria widely distributed in nature. It has been isolated from sewage, soil, silage, and from feces of healthy animals and man. Infection with this bacterium leads to encephalitis, meningitis, endocarditis, and abortion.Immunity, Innate: The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.Adaptive Immunity: Protection from an infectious disease agent that is mediated by B- and T- LYMPHOCYTES following exposure to specific antigen, and characterized by IMMUNOLOGIC MEMORY. It can result from either previous infection with that agent or vaccination (IMMUNITY, ACTIVE), or transfer of antibody or lymphocytes from an immune donor (IMMUNIZATION, PASSIVE).Tetanus Toxin: Protein synthesized by CLOSTRIDIUM TETANI as a single chain of ~150 kDa with 35% sequence identity to BOTULINUM TOXIN that is cleaved to a light and a heavy chain that are linked by a single disulfide bond. Tetanolysin is the hemolytic and tetanospasmin is the neurotoxic principle. The toxin causes disruption of the inhibitory mechanisms of the CNS, thus permitting uncontrolled nervous activity, leading to fatal CONVULSIONS.Lipopolysaccharides: Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis.Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.Membrane Proteins: 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.

A cytomegalovirus glycoprotein re-routes MHC class I complexes to lysosomes for degradation. (1/5439)

Mouse cytomegalovirus (MCMV) early gene expression interferes with the major histocompatibility complex class I (MHC class I) pathway of antigen presentation. Here we identify a 48 kDa type I transmembrane glycoprotein encoded by the MCMV early gene m06, which tightly binds to properly folded beta2-microglobulin (beta2m)-associated MHC class I molecules in the endoplasmic reticulum (ER). This association is mediated by the lumenal/transmembrane part of the protein. gp48-MHC class I complexes are transported out of the ER, pass the Golgi, but instead of being expressed on the cell surface, they are redirected to the endocytic route and rapidly degraded in a Lamp-1(+) compartment. As a result, m06-expressing cells are impaired in presenting antigenic peptides to CD8(+) T cells. The cytoplasmic tail of gp48 contains two di-leucine motifs. Mutation of the membrane-proximal di-leucine motif of gp48 restored surface expression of MHC class I, while mutation of the distal one had no effect. The results establish a novel viral mechanism for downregulation of MHC class I molecules by directly binding surface-destined MHC complexes and exploiting the cellular di-leucine sorting machinery for lysosomal degradation.  (+info)

Crystal structure of an MHC class I presented glycopeptide that generates carbohydrate-specific CTL. (2/5439)

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)

Generation of CD8(+) T-cell responses to Mycobacterium bovis and mycobacterial antigen in experimental bovine tuberculosis. (3/5439)

Protective immunity against tuberculosis is considered to be essentially cell mediated, and an important role for CD8(+) T lymphocytes has been suggested by several studies of murine and human infections. The present work, using an experimental model of infection with Mycobacterium bovis in cattle, showed that live M. bovis elicits the activation of CD8(+) T cells in vitro. However, a sonic extract prepared from M. bovis (MBSE) and protein purified derivative (PPDb) also induced a considerable degree of activation of the CD8(+) T cells. Analysis of proliferative responses of peripheral blood mononuclear cells, purified CD8(+) T cells, and CD8(+) T-cell clones to M. bovis and to soluble antigenic preparations (MBSE, PPDb) showed that the responses of all three types of cells were always superior for live mycobacteria but that strong responses were also obtained with complex soluble preparations. Furthermore, while cytotoxic capabilities were not investigated, the CD8(+) T cells were found to produce and release gamma interferon in response to antigen (live and soluble), which indicated one possible protective mechanism for these cells in bovine tuberculosis. Finally, it was demonstrated by metabolic inhibition with brefeldin A and cytochalasin D at the clonal level that an endogenous pathway of antigen processing is required for presentation to bovine CD8(+) cells and that presentation is also dependent on phagocytosis of the antigen.  (+info)

Interleukin-10-treated human dendritic cells induce a melanoma-antigen-specific anergy in CD8(+) T cells resulting in a failure to lyse tumor cells. (4/5439)

Dendritic cells (DC) are critically involved in the initiation of primary immune processes, including tumor rejection. In our study, we investigated the effect of interleukin-10 (IL-10)-treated human DC on the properties of CD8(+) T cells that are known to be essential for the destruction of tumor cells. We show that IL-10-pretreatment of DC not only reduces their allostimulatory capacity, but also induces a state of alloantigen-specific anergy in both primed and naive (CD45RA+) CD8(+) T cells. To investigate the influence of IL-10-treated DC on melanoma-associated antigen-specific T cells, we generated a tyrosinase-specific CD8(+) T-cell line by several rounds of stimulation with the specific antigen. After coculture with IL-10-treated DC, restimulation of the T-cell line with untreated, antigen-pulsed DC demonstrated peptide-specific anergy in the tyrosinase-specific T cells. Addition of IL-2 to the anergic T cells reversed the state of both alloantigen- or peptide-specific anergy. In contrast to optimally stimulated CD8(+) T cells, anergic tyrosinase-specific CD8(+) T cells, after coculture with peptide-pulsed IL-10-treated DC, failed to lyse an HLA-A2-positive and tyrosinase-expressing melanoma cell line. Thus, our data demonstrate that IL-10-treated DC induce an antigen-specific anergy in cytotoxic CD8(+) T cells, a process that might be a mechanism of tumors to inhibit immune surveillance by converting DC into tolerogenic antigen-presenting cells.  (+info)

Presentation of renal tumor antigens by human dendritic cells activates tumor-infiltrating lymphocytes against autologous tumor: implications for live kidney cancer vaccines. (5/5439)

The clinical impact of dendritic cells (DCs) in the treatment of human cancer depends on their unique role as the most potent antigen-presenting cells that are capable of priming an antitumor T-cell response. Here, we demonstrate that functional DCs can be generated from peripheral blood of patients with metastatic renal cell carcinoma (RCC) by culture of monocytes/macrophages (CD14+) in autologous serum containing medium (RPMI) in the presence of granulocyte macrophage colony-stimulating factor and interleukin (IL) 4. For testing the capability of RCC-antigen uptake and processing, we loaded these DCs with autologous tumor lysate (TuLy) using liposomes, after which cytometric analysis of the DCs revealed a markedly increased expression of HLA class I antigen and a persistent high expression of class II. The immunogenicity of DC-TuLy was further tested in cultures of renal tumor infiltrating lymphocytes (TILs) cultured in low-dose IL-2 (20 Biologic Response Modifier Program units/ml). A synergistic effect of DC-TuLy and IL-2 in stimulating a T cell-dependent immune response was demonstrated by: (a) the increase of growth expansion of TILs (9.4-14.3-fold; day 21); (b) the up-regulation of the CD3+ CD56- TcR+ (both CD4+ and CD8+) cell population; (c) the augmentation of T cell-restricted autologous tumor lysis; and (d) the enhancement of IFN-gamma, tumor necrosis factor-alpha, granulocyte macrophage colony-stimulating factor, and IL-6 mRNA expression by TILs. Taken together, these data implicate that DC-TuLy can activate immunosuppressed TIL via an induction of enhanced antitumor CTL responses associated with production of Thl cells. This indicates a potential role of DC-TuLy vaccines for induction of active immunity in patients with advanced RCC.  (+info)

Identification of MAGE-3 epitopes presented by HLA-DR molecules to CD4(+) T lymphocytes. (6/5439)

MAGE-type genes are expressed by many tumors of different histological types and not by normal cells, except for male germline cells, which do not express major histocompatibility complex (MHC) molecules. Therefore, the antigens encoded by MAGE-type genes are strictly tumor specific and common to many tumors. We describe here the identification of the first MAGE-encoded epitopes presented by histocompatibility leukocyte antigen (HLA) class II molecules to CD4(+) T lymphocytes. Monocyte-derived dendritic cells were loaded with a MAGE-3 recombinant protein and used to stimulate autologous CD4(+) T cells. We isolated CD4(+) T cell clones that recognized two different MAGE-3 epitopes, MAGE-3114-127 and MAGE-3121-134, both presented by the HLA-DR13 molecule, which is expressed in 20% of Caucasians. The second epitope is also encoded by MAGE-1, -2, and -6. Our procedure should be applicable to other proteins for the identification of new tumor-specific antigens presented by HLA class II molecules. The knowledge of such antigens will be useful for evaluation of the immune response of cancer patients immunized with proteins or with recombinant viruses carrying entire genes coding for tumor antigens. The use of antigenic peptides presented by class II in addition to peptides presented by class I may also improve the efficacy of therapeutic antitumor vaccination.  (+info)

Calreticulin, a peptide-binding chaperone of the endoplasmic reticulum, elicits tumor- and peptide-specific immunity. (7/5439)

Calreticulin (CRT), a peptide-binding heat shock protein (HSP) of the endoplasmic reticulum (ER), has been shown previously to associate with peptides transported into the ER by transporter associated with antigen processing (Spee, P., and J. Neefjes. 1997. Eur. J. Immunol. 27: 2441-2449). Our studies show that CRT preparations purified from tumors elicit specific immunity to the tumor used as the source of CRT but not to an antigenically distinct tumor. The immunogenicity is attributed to the peptides associated with the CRT molecule and not to the CRT molecule per se. It is further shown that CRT molecules can be complexed in vitro to unglycosylated peptides and used to elicit peptide-specific CD8(+) T cell response in spite of exogenous administration. These characteristics of CRT closely resemble those of HSPs gp96, hsp90, and hsp70, although CRT has no apparent structural homologies to them.  (+info)

Maturation, activation, and protection of dendritic cells induced by double-stranded RNA. (8/5439)

The initiation of an immune response is critically dependent on the activation of dendritic cells (DCs). This process is triggered by surface receptors specific for inflammatory cytokines or for conserved patterns characteristic of infectious agents. Here we show that human DCs are activated by influenza virus infection and by double-stranded (ds)RNA. This activation results not only in increased antigen presentation and T cell stimulatory capacity, but also in resistance to the cytopathic effect of the virus, mediated by the production of type I interferon, and upregulation of MxA. Because dsRNA stimulates both maturation and resistance, DCs can serve as altruistic antigen-presenting cells capable of sustaining viral antigen production while acquiring the capacity to trigger naive T cells and drive polarized T helper cell type 1 responses.  (+info)

*Antigen-presenting cell

... antigen presentation relies on other specialized signaling molecules on the surfaces of both APCs and T cells. Antigen- ... DCs present antigen to both helper and cytotoxic T cells. They can also perform cross-presentation, a process by which they ... Antigen presentation allows for specificity of adaptive immunity and can contribute to immune responses against both ... However, it has been observed that antigen presentation to CD4+ cells via MHC class II is not restricted to the classically ...

*HLA-DOB

HLA class II histocompatibility antigen, DO beta chain is a protein that in humans is encoded by the HLA-DOB gene. HLA-DOB ... 1993). "HIV-1 envelope protein is expressed on the surface of infected cells before its processing and presentation to class II ... 1992). "DNA sequence analysis of 66 kb of the human MHC class II region encoding a cluster of genes for antigen processing". J ... 1994). "HLA class II antigens and the HIV envelope glycoprotein gp120 bind to the same face of CD4". J. Immunol. 152 (9): 4475- ...

*HLA-DOA

HLA class II histocompatibility antigen, DO alpha chain is a protein that in humans is encoded by the HLA-DOA gene. HLA-DOA ... 1993). "HIV-1 envelope protein is expressed on the surface of infected cells before its processing and presentation to class II ... 1994). "HLA class II antigens and the HIV envelope glycoprotein gp120 bind to the same face of CD4". J. Immunol. 152 (9): 4475- ... 1991). "Interaction of CD4 with HLA class II antigens and HIV gp120". Immunogenetics. 34 (2): 121-8. doi:10.1007/BF00211424. ...

*HLA-F

... of HLA class I and they function together in cross-presentation of exogenous antigen. Exogenous antigen binds to a structure on ... it is involved in cross-presentation of exogenous antigen. The complex HLA-F/HLA class-I OC is a ligand for a subset of KIR ( ... "HLA-F and MHC-I open conformers cooperate in a MHC-I antigen cross-presentation pathway". Journal of Immunology. 191 (4): 1567- ... Zhang X, Lin A, Zhang JG, Bao WG, Xu DP, Ruan YY, Yan WH (January 2013). "Alteration of HLA-F and HLA I antigen expression in ...

*Tapasin

... is a MHC class I antigen-processing molecule present in the lumen of the endoplasmic reticulum. It plays an important ... Howarth M, Williams A, Tolstrup AB, Elliott T (August 2004). "Tapasin enhances MHC class I peptide presentation according to ... Tapasin has been shown to interact with: HLA-A, and TAP1 Transporter associated with antigen processing ("TAP") ENSG00000236490 ... Tissue Antigens. 52 (3): 279-81. doi:10.1111/j.1399-0039.1998.tb03044.x. PMID 9802609. El Ouakfaoui S, Heitz D, Paquin R, ...

*MHC class I

It is in this way, the MHC class I-dependent pathway of antigen presentation, that the virus infected cells signal T-cells that ... Hewitt, E.W. (2003). "The MHC class I antigen presentation pathway: strategies for viral immune evasion". Immunology. 110 (2): ... "Exogenous antigens are processed through the endoplasmic reticulum-associated degradation (ERAD) in cross-presentation by ... Histocompatibility Antigens Class I at the US National Library of Medicine Medical Subject Headings (MeSH) MHC Class I Genes at ...

*Antigen presentation

... protein/protein interactions and more for genes involved in antigen processing and presentation antigen presentation at the US ... Because T cells recognise only fragmented antigens displayed on cell surfaces, antigen processing must occur before the antigen ... Cross-presentation is a special case in which MHC-I molecules are able to present extracellular antigens, usually displayed ... This antigen presentation pathway enables the immune system to detect transformed or infected cells displaying peptides from ...

*Diffuse panbronchiolitis

... "antigen presentation". The infected cells then become targets for types of cytotoxic T-cells, which kill the infected cells so ... A subset of MHC in humans is human leukocyte antigen (HLA), which controls the antigen-presenting system, as part of adaptive ... its genes and their roles in antigen presentation. 15. Pergamon. Keicho, N.; Hijikata, M. (May 2011). "Genetic predisposition ... Online Mendelian Inheritance in Man (OMIM) Human Leukocyte Antigen A -142800 Retrieved 21 September 2011. Azuma, A.; Kudoh, S ...

*CD4+ T cells and antitumor immunity

... through activation of antigen presenting cells (APCs) and increased antigen presentation on MHC class I, as well as secretion ... This can be attributed to a number of things; CD4+ T cells respond only to presentation of antigens by MHC class II, however, ... Cancer cells, through mutation, may actually have mutations in some of the proteins involved in antigen presentation, and as ... The simplest approach involves upregulation of adhesion molecules, thus extending the presentation of antigens by APC ( ...

*TAP1

Gobin SJ, Wilson L, Keijsers V, Van den Elsen PJ (1997). "Antigen processing and presentation by human trophoblast-derived cell ... Townsend A, Trowsdale J (1993). "The transporters associated with antigen presentation". Semin. Cell Biol. 4 (1): 53-61. doi: ... "Presentation of viral antigen controlled by a gene in the major histocompatibility complex". Nature. 345 (6274): 449-52. doi: ... "A functionally defective allele of TAP1 results in loss of MHC class I antigen presentation in a human lung cancer". Nat. Genet ...

*TAP2

The protein encoded by this gene is involved in antigen presentation. This protein forms a heterodimer with ABCB2 in order to ... "The transporters associated with antigen presentation". Semin. Cell Biol. 4 (1): 53-61. doi:10.1006/scel.1993.1007. PMID ... TAP2 is a gene in humans that encodes the protein Antigen peptide transporter 2. The membrane-associated protein encoded by ... WHO Nomenclature Committee for factors of the HLA system". Tissue Antigens. 39 (4): 161-73. doi:10.1111/j.1399-0039.1992. ...

*Histiocyte

... phagocytosis and antigen presentation. Phagocytosis is the main process of macrophages and antigen presentation the main ... Their main activity is antigen presentation; they express Factor XIIIa, CD1c, and Class II Human leukocyte antigens. A subset ... Langerhans cells are antigen-presenting cells but have undergone further differentiation. Skin Langerhans cells express CD1a, ... They express LCAs (leucocyte common antigens) CD45, CD14, CD33, and CD4 (also expressed by T helper cells). These histiocytes ...

*CD96

It may also function in antigen presentation. Alternative splicing occurs at this locus and two transcript variants encoding ...

*Macrophage polarization

Antigen presentation is upregulated (MHC II, CD86). M2c macrophages are important for secretion of IL-10, TGF-β. They also ... specific chemokines and antigen presentation molecules). M1 macrophages are irreplaceable during acute infectious diseases and ... Ability of TAMs to present tumour-associated antigens is decreased as well as stimulation of the anti-tumour functions of T and ...

*Transporter associated with antigen processing

Janeway CA, Travers P, Walport M, Shlomchik M (2001). "Chapter 5, Antigen Presentation to T-lymphocytes". In Janeway, Charles. ... Transporter associated with antigen processing (TAP) is a member of the ATP-binding-cassette transporter family. It delivers ... transporter associated with antigen processing (TAP) at the US National Library of Medicine Medical Subject Headings (MeSH). ... Lankat-Buttgereit B, Tampé R (2002). "The transporter associated with antigen processing: function and implications in human ...

*Apolipoprotein E

... lipid antigen presentation facilitation (by CD1) to natural killer T cell as well as modulation of inflammation and oxidation. ... "Apolipoprotein-mediated pathways of lipid antigen presentation". Nature. 437 (7060): 906-10. doi:10.1038/nature04001. PMID ...

*CD1E

The CD1 proteins mediate the presentation of primarily lipid and glycolipid antigens of self or microbial origin to T cells. ... "Entrez Gene: CD1E CD1e molecule". Brigl M, Brenner MB (2004). "CD1: antigen presentation and T cell function". Annu. Rev. ... CD1E Antigen at the US National Library of Medicine Medical Subject Headings (MeSH) Human CD1A genome location and CD1A gene ... Yu CY, Milstein C (1990). "A physical map linking the five CD1 human thymocyte differentiation antigen genes". EMBO J. 8 (12): ...

*CD1D

Melián A, Beckman EM, Porcelli SA, Brenner MB (1996). "Antigen presentation by CD1 and MHC-encoded class I-like molecules". ... Brigl M, Brenner MB (2004). "CD1: antigen presentation and T cell function". Annu. Rev. Immunol. 22 (1): 817-90. doi:10.1146/ ... and are involved in the presentation of lipid antigens to T cells. CD1d is the only member of the group 2 CD1 molecules. CD1d- ... iGb3, a self antigen which has been implied in iNKT selection. HS44, a synthetic amino cyclitolic ceramide analogue which has ...

*CD1A

The CD1 proteins mediate the presentation of primarily lipid and glycolipid antigens of self or microbial origin to T cells. ... Melián A, Beckman EM, Porcelli SA, Brenner MB (1996). "Antigen presentation by CD1 and MHC-encoded class I-like molecules". ... Brigl M, Brenner MB (2004). "CD1: antigen presentation and T cell function". Annu. Rev. Immunol. 22 (1): 817-90. doi:10.1146/ ... 2000). "Separate pathways for antigen presentation by CD1 molecules". Immunity. 11 (6): 743-52. doi:10.1016/S1074-7613(00)80148 ...

*Phagosome

Savina, Ariel; Amigorena, Sebastian (October 2007). "Phagocytosis and antigen presentation in dendritic cells". Immunological ... as DCs are mainly involved in antigen presentation rather than pathogen degradation. They need to retain protein fragments of a ... Peptides from the bacteria are trafficked to the Major Histocompatibility Complex (MHC). The peptide antigens are presented to ...

*Psychoneuroimmunology

Suppress cell adhesion, antigen presentation, chemotaxis and cytotoxicity. Increase apoptosis. Release of corticotropin- ... They found that the immune responses to innocuous antigens triggers an increase in the activity of hypothalamic neurons and ...

*Skin immunity

Antigen presentation may occur in peripheral lymphoid tissues. The Langerhans cells, once they are activated, they rapidly ... The epidermis antigens are connected with some cells of the skin. Among them there are the APC, antigen presenting cells ( ... Once the activated lymphocytes arrive, they get in contact with the antigen, they proliferate and develop their effector ... and present the antigens to T lymphocytes in local lymphoid organs. As result, T lymphocytes express the CLA molecule. ...

*Monocyte

These are phagocytosis, antigen presentation, and cytokine production. Phagocytosis is the process of uptake of microbes and ... This process is called antigen presentation and it leads to activation of T lymphocytes, which then mount a specific immune ... Microbial fragments that remain after such digestion can serve as antigens. The fragments can be incorporated into MHC ... response against the antigen. Other microbial products can directly activate monocytes and this leads to production of pro- ...

*Halobacterium

Stuart, Elizabeth S.; Morshed, Fazeela; Sremac, Marinko; DasSarma, Shiladitya (15 June 2001). "Antigen presentation using novel ...

*Gas vesicle

Stuart, E. S.; Morshed, F.; Sremac, M.; DasSarma, S. (2001-06-15). "Antigen presentation using novel particulate organelles ... Several antigens from various human pathogens have been recombined into the gvpC gene to create subunit vaccines with long- ... Potential vaccines using gas vesicle as an antigen display can be given via the mucosal route as an alternative administration ... "Haloarchaeal Gas Vesicle Nanoparticles Displaying Salmonella Antigens as a Novel Approach to Vaccine Development". Procedia in ...

*PSMD7

... proteins are digested into peptides for MHC class I antigen presentation. To meet such complicated demands in biological ... the HIV-1 Tat protein and the 11S regulator subunit alpha is crucial for their effects on proteasome function including antigen ...

*Phagocyte

... stimulate lymphocytes to produce antibodies by an important process called antigen presentation. Antigen presentation is a ... Mast cells express MHC class II molecules and can participate in antigen presentation; however, the mast cell's role in antigen ... After phagocytosis, macrophages and dendritic cells can also participate in antigen presentation, a process in which a ... "Antigen presentation and T cell stimulation by dendritic cells". Annu. Rev. Immunol. 20: 621-67. doi:10.1146/annurev.immunol. ...
After viral infection, cells rapidly present peptides derived from newly synthesized viral proteins on MHC class I molecules for T cell activation (1). This rapidity of presentation, coupled with the relatively long half-life (t1/2) of most viral proteins, engendered the defective ribosomal product (DRiP) hypothesis of Ag presentation: a subset of newly synthesized proteins are defective in some manner and rapidly degraded intracellularly, yielding peptides for MHC class I Ag presentation to enable rapid immunosurveillance of viral and cellular translation products (2).. More than a decade after the birth of the DRiP hypothesis, there are only a few clues regarding the physical and biochemical properties of DRiPs that give rise to class I peptide ligands (3). Although large amounts of rapidly degraded polypeptides (RDPs) are relatively easy to detect (3-6), their relationship with DRiPs is uncertain (3, 7). The DRiP hypothesis is strongly supported, however, by functional studies that temporally ...
TY - JOUR. T1 - Dendritic cell/macrophage precursors capture exogenous antigen for MHC class I presentation by dendritic cells. AU - Mitchell, Duane A.. AU - Nair, Smita K.. AU - Gilboa, Eli. PY - 1998/6/1. Y1 - 1998/6/1. N2 - Presentation of MHC class I antigens by professional antigen-presenting cells (APC) is an important pathway in priming cytotoxic T lymphocyte responses in vivo. This study sought to identify the nature of the professional APC responsible for indirect class I presentation by examining a special feature of professional APC, namely their ability to process exogenous forms of antigen for class I presentation. Incubation of highly purified bone marrow-derived precursor cells with chicken ovalbumin (OVA) led to the efficient presentation of the major class I-restricted OVA determinant by mature dendritic cells (DC), but not by macrophages (MΦ) derived from the precursor population. DC as well as macrophages were, however, able to mediate class II presentation of OVA, suggesting ...
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In the current study, we investigated the requirements of MHC I presentation during Chlamydia infection using C57BL/6 mice, the mouse DC line JAWS II, and the nonavian C. psittaci (DC15) as an infection model system. The most intriguing finding of our work is that autophagy constitutes a critical pathway in MHC I processing of chlamydial Ags in infected DCs.. Our data demonstrate that the disease in C. psittaci-infected C57BL/6 mice is comparable to what was recently described for infected cattle (37), the natural host of C. psittaci strain DC15. In particular, the onset of the most pronounced clinical signs due to bronchopneumonia, the pathological features, and the course of disease are remarkably similar. Chlamydia-infected DCs show morphological, as well as functional, maturation, which is characterized by elevated expression of distinct activation/maturation markers and secretion of chemokines/cytokines known to be associated with optimal Ag presentation and clearance of bacterial ...
Abstract It is widely appreciated that inflammatory responses in peripheral tissues are usually associated to the development of acidic microenvironments. Despite this, there are f..
It is generally assumed that the MHC class I antigen (Ag)-processing (CAP) machinery - which supplies peptides for presentation by class I molecules - plays no role in class II-restricted presentation of cytoplasmic Ags. In striking contrast to this
Over the last decade, our understanding and ability to predict the MHC class I pathway antigen presentation has improved substantially. This however does not hold for post-transnationally modified (PTM) antigens, where our understanding on how PTMs impact the potential for antigen presentation remains limited. Likewise, is our ability to predict MHC class II antigen presentation limited, and data suggest that properties other that MHC binding plays a critical role for the prediction of CD4 epitopes. Finally, is our understanding of the role of the T cell and the similarity of the presented peptide to the self proteome in the context of peptide immunogenicity very limited ...
Introduction: Despite the unrecognized nature of fetal antigens for maternal immune system, the fetus is usually not rejected and is rather sustained by maternal imm...
Background Tapasin is a crucial component of the major histocompatibility (MHC) class I antigen presentation pathway. The downregulation of the MHC I complex reduces the immunogenicity of tumors. We hypothesized that the expression of Tapasin may predict immune infiltration of colorectal cancer (CRC) by CD8+ cytotoxic T lymphocytes (CTLs) and overall survival. In vitro, the expression of Tapasin can be rescued by cytokine treatment, indicating that the misregulation is neither genetic nor structural and may occur on an epigenetic level. We therefore tested the possible involvement of the RNA silencing protein Dicer in the post-transcriptional regulation of Tapasin expression.. Methods Resection specimens from 219 CRC patients with full clinicopathological information were included in this study. ngTMA (next generation tissue microarray) slides containing 8 punches from each case (tumor and normal tissue) were immunostained for MHC I pathway components (MHC I, beta-2-microglobuline, Calnexin, ...
Whole protein delivery to B-cells by cell squeezing enables robust MHC class I antigen presentation and antigen-specific CD8+T-cell priming in vitro.. A) Experimental timeline for antigen loading (endocytosis, peptide, or squeezed) on day 0 followed by co-culture with purified, CFSE-labelled OT-I CD8+T-cells. B) Representative histogram overlay showing data from day 4 proliferation of endocytosis+CpG or SQZ+CpG co-cultures; green gates were used to calculate percent of divided input cells and proliferation indices as described in Methods. C,D) Quantitative analysis of percent divided input OT-I CD8+(C) and OT-II CD4+(D) T-cells at day 4 of co-culture. E) Normalized total OT-I CD8+T-cell counts on day 4 of co-cultures were also calculated as described in Methods. All data were shown as means±standard deviation (n = 7 independent experiments for B & D; n = 3 independent experiments for D). Pairs of conditions were tested in C), D) and E) for statistically significant pairwise differences with ...
Thymocytes adoptively transferred into syngeneic irradiated recipients can be primed with antigen (KLH) to generate two types of helper function termed specific and non-specific. Low doses of KLH given without adjuvant generate high levels of non-specific compared to specific helper T cells. Large doses of KLH given in adjuvant (FCA) generate high levels of both types of helper T cell. Explantations for this observation are discussed.
Das Proteasom ist eine ATP- abhängige Protease, die sich aus vielen Untereinheiten zusammensetzt. Es ist für die Generierung der MHC Klasse I- restringierten Peptide verantwortlich, die im Folgenden auf der Zelloberfläche präsentiert werden. Nicht-funktionelle Proteine, die als so genannte defective ribosomal products (DRIP) bezeichnet werden, stellen eine wichtige Quelle für die Generierung von antigenen Peptiden, insbesondere jedoch von viralen Peptiden dar. Generell wird die Lehrmeinung vertreten, dass der Abbau von polyubiquitinierten Proteinen durch das 26S Proteasom zur Generierung von MHC Klasse I- Liganden führt. Allerdings ist weiterhin unklar, ob virale Proteine Ubiquitin- abhängig vom Proteasom abgebaut werden. Demnach sollte im Rahmen dieser Arbeit der Proteasom- abhängige Abbau des mCMV ie pp89 Proteins vor allem hinsichtlich einer Ubiquitinierung untersucht werden. Folglich wurden Konstrukte sowohl für ein rekombinantes pp89 (rek pp89) als auch für ein ODCpp89 ...
Das Proteasom ist eine ATP- abhängige Protease, die sich aus vielen Untereinheiten zusammensetzt. Es ist für die Generierung der MHC Klasse I- restringierten Peptide verantwortlich, die im Folgenden auf der Zelloberfläche präsentiert werden. Nicht-funktionelle Proteine, die als so genannte defective ribosomal products (DRIP) bezeichnet werden, stellen eine wichtige Quelle für die Generierung von antigenen Peptiden, insbesondere jedoch von viralen Peptiden dar. Generell wird die Lehrmeinung vertreten, dass der Abbau von polyubiquitinierten Proteinen durch das 26S Proteasom zur Generierung von MHC Klasse I- Liganden führt. Allerdings ist weiterhin unklar, ob virale Proteine Ubiquitin- abhängig vom Proteasom abgebaut werden. Demnach sollte im Rahmen dieser Arbeit der Proteasom- abhängige Abbau des mCMV ie pp89 Proteins vor allem hinsichtlich einer Ubiquitinierung untersucht werden. Folglich wurden Konstrukte sowohl für ein rekombinantes pp89 (rek pp89) als auch für ein ODCpp89 ...
In this first serologic case-control study of MCV infection and SCC, MCV seroreactivity was statistically significantly associated with MCV DNA-positive SCC. There are several possible explanations for the observed serologic associations. MCV seroreactivity could simply be a marker of a general systemic immunosuppression, an established risk factor for SCC. If this was the case, then associations with SCC would be expected to be observed also for JCV seroreactivity, given that JCV reactivates with immunosuppression (20). Although a greater proportion of SCC cases were JCV-seropositive than controls, the difference was not statistically significant, and no trend was observed between increasing quartiles of JCV antibody levels and SCC risk. Uncontrolled MCV replication resulting from localized cutaneous immunosuppression is theoretically possible, given the previously described effects of UV radiation on antigen presentation and cytokine production in the skin (21-24). However, no associations ...
3 Stigma Stigma can be caused by many factors including: Family/social group views of psychological health Prior experience with mental health services Views expressed/demonstrated by peers Views expressed/demonstrated by leaders
... is an immunological process that prepares antigens for presentation to special cells of the immune system called T lymphocytes. It is considered to be a stage of antigen presentation pathways. The process by which antigen-presenting cells digest proteins from inside or outside the cell and display the resulting antigenic peptide fragments on cell surface MHC molecules for recognition by T cells is central to the bodys ability to detect signs of infection or abnormal cell growth. As such, understanding the processes and mechanisms of antigen processing and presentation provides us with crucial insights necessary for the design of vaccines and therapeutic strategies to bolster T-cell responses.. ...
Ubiquitin-Dependent Control of Class II MHC Localization Is Dispensable for Antigen Presentation and Antibody Production. . 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.
The following presentations were recorded during the APS Annual Meeting in Pasadena, CA, August 1-5, 2015. ​ Presentations are grouped by Session Title. To view the presentation titles use the image to expand/collapse....
The IFNE Congress 2017 Committee thanks all faculty and delegates for their support and contributions to the success of the 2017 meeting. Consented presentations are available for your interest below. Click on the author name and presentation title to download.. Benjamin Wharf - Saving Lives and growing brains ...
Presentations are one of the first managerial skills which a junior engineer must acquire. This article looks at the basics of Presentation Skills as
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The informal research seminar of the ALGO and AGA groups. Talks last roughly 25 minutes, with five extra minutes allocated for discussion. Many presentations are focussed on recent conference presentations, or practice talks for upcoming conferences. New members are often asked to give an overview of their field of research. Talks given by invited speakers may take up to 45-60 minutes including questions.. To be kept up-to-date about noon seminar presentations, please subscribe to the algoseminar-l mailing list.. All noon seminar schedules: 2018 · 2017 · 2016 · 2015 · 2014 · 2013 · 2012 · 2011 · 2010 · 2009 · 2008 · 2007 · 2006 · 2005. ...
The informal research seminar of the ALGO and AGA groups. Talks last roughly 25 minutes, with five extra minutes allocated for discussion. Many presentations are focussed on recent conference presentations, or practice talks for upcoming conferences. New members are often asked to give an overview of their field of research. Talks given by invited speakers may take up to 45-60 minutes including questions.. To be kept up-to-date about noon seminar presentations, please subscribe to the algoseminar-l mailing list.. All noon seminar schedules: 2018 · 2017 · 2016 · 2015 · 2014 · 2013 · 2012 · 2011 · 2010 · 2009 · 2008 · 2007 · 2006 · 2005. ...
Full development of the approved capstone project. The strategies set forth in the proposal are put into action: developing a research concept, solving a strategic management challenge, or launching an entrepreneurial business. Primary data using quantitative and qualitative methods are a required part of the project. Oral and formal presentations are required. Taken in the final semester of the MBA program. Prerequisite: successful completion of all foundation and core MBA courses, inclusive of MBA 6450 or NUR 5670. Corequisite for Nursing Administration students: NUR 6310 ...
Full development of the approved capstone project. The strategies set forth in the proposal are put into action: developing a research concept, solving a strategic management challenge, or launching an entrepreneurial business. Primary data using quantitative and qualitative methods are a required part of the project. Oral and formal presentations are required. Taken in the final semester of the MBA program. Prerequisite: successful completion of all foundation and core MBA courses, inclusive of MBA 6450 or NUR 5670. Corequisite for Nursing Administration students: NUR 6310 ...
Everything is going more virtual these days. TBOOKS stays paper. So youll never find a publication online. The publications are handmade in alternative print techniques. , cause sales money will be invested in another publication. Following this, the aim of TBOOKS is to have affordable prices for the publications. Accessible prices combined with high quality content and a devoted presentation are what constitutes TBOOKS COLOGNE. ...
Note: All presentations are scheduled for 10 minutes, including setup and questions, and should be targetted towards the discussion topics for the session. At the end of each technical session there will be a discussion period ...
So guys, E3 presentations are over for the big guys. And wouw what a ride! Microsoft kicked it this year and it made me go from YES! To OMG to WOUW!...
Background The MHC molecules are glycoproteins encoded in a large cluster of genes located on chromosome 6. They were first identified by their potent
Presentation on Results for the 1st Quarter FY 2014 Idemitsu Kosan Co.,Ltd. August 5, 2014 Table of Contents 1. FY st Quarter Financials (1) Overview (2) Segment Information (3) Streamlining (4)
Please provide below the URL and description of an activity you would like to add to OpenCME. You are welcome to add activities as often as you like. To prevent spam or other abuse, activities are reviewed by our editorial team before appearing on OpenCME. ...
In this new paper by Nir Hacohen et al., researchers found that by analyzing the DNA of tumors from patients who developed resistance to checkpoint therapy, they found changes in the DNA of a key gene that is critical for tumors to be detected by the immune system.
Design of the British Gas presentation for the successful media pitch by Carat. Creation of a main template with all the graphic assets, colour palette and images reflecting the brand value. Production of all elements for the deck including icons, charts …
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Dear all, The main purpose of this site is to educate and inform those with this disease. There are so many questions as this is a complex disease. Attached is a video presentation given by Dr Gavin Giovannoni - he ...
Download DNA Computing PPT Presentation .The main objective of this paper is to give idea of DNA computing. The framework which is being used from the room sized
2 presentations will be held in ICMU2017 - センサ・デバイス・ネットワークが連携し、センサから取り 込まれる実世界データを処理・集約・解析することで、高度なサービスを 効率良くユーザに提供するシステム―ユビキタスコンピューティングシス テム―の実現に向けた研究に取り組んでいます。
Overloaded. Groups the elements of a sequence according to a specified key selector function and creates a result value from each group and its key. Key values are compared by using a specified comparer, and the elements of each group are projected by using a specified function.(Defined by Enumerable.) ...
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+Analysis andIsolation ofPlasminogenActivator fromMammalian CellCulture BrothDelaine Zayas-Bazán BurgosJohn Muñoz TorresVibha Bansal PhDMr. Javier RosadoMr. Ca…
医薬品・医療機器・再生医療等製品の承認審査・安全対策・健康被害救済の3つの業務を行う組織。
Newly synthesised major histocompatibility complex class II molecules associate with invariant chains (Ii) to form nonameric complexes. These complexes are transported to endosomes, where proteolytic enzymes generate alphabeta class II dimers associated with nested Ii-derived peptides. These peptides are then exchanged with antigen peptide, and mature class II molecules reach the cell surface. The role of the actin cytoskeleton in the transport and maturation of class II molecules has not been studied. We show here that upon treatment with cytochalasin D (cyto D), the rate of Ii degradation is drastically reduced in B cells. Cyto D treatment also leads to a delayed appearance of stable forms of class II molecules, and a reduced presentation efficiency of antigen determinants requiring newly synthesised class II molecules. Under such conditions, we found that invariant chain fragments and class II molecules are accumulated in early and late endosomal compartments, whereas the leupeptin protease ...
Antigen presenting cells (APCs) such as B cells, dendritic cells (DCs) and monocytes/macrophages express major histocompatibility complex class II molecules (MHC II) at their surface and present exogenous antigenic peptides to CD4+ T helper cells. CD4+ T cells play a central role in immune protection. On their activation they stimulate differentiation of B cells into antibody-producing B-cell blasts and initiate adaptive immune responses. MHC class II molecules are transmembrane glycoprotein heterodimers of alpha and beta subunits. Newly synthesized MHC II molecules present in the endoplasmic reticulum bind to a chaperone protein called invariant (Ii) chain. The binding of Ii prevents the premature binding of self antigens to the nascent MHC molecules in the ER and also guides MHC molecules to endocytic compartments. In the acidic endosomal environment, Ii is degraded in a stepwise manner, ultimately to free the class II peptide-binding groove for loading of antigenic peptides. Exogenous ...
Figure 4. pDCs recruited to LNs during EAE establish Ag-specific interactions with CD4+ T cells. (A) WT and pIII+IV−/− mice were injected with CFA and dLNs were harvested after 2 d. dLN sections from untreated and CFA-treated mice were stained with antibodies against PNAd to label HEVs and PDCA-1 to label pDCs. Histograms show the density (percentage of surface) of pDCs in regions situated near to (,20 µm) or distant from (,20 µm) HEVs. Results are representative of three independent experiments. The means and SEM derived from three independent mice per group are shown. ns, not significant; *, P , 0.05; **, P , 0.01. 7-12 confocal images were analyzed for each genotype and region. Representative images are shown. (B) CMTMR-labeled 2D2 CD4+ T cells were adoptively transferred into WT and pIII+IV−/− mice that had been injected 1 d previously with MOG35-55+CFA or CFA alone. dLNs were harvested 1 d after the T cell transfer, and sections were stained with antibodies against PDCA-1. ...
0173]MHC Class I Antigen Presentation Assay. The ability of the polymer to increase cytoplasmic delivery and subsequent MHC class I antigen presentation was evaluated using the lacZ antigen presentation assay. This assay utilizes a specialized LacZ B3Z CTL hybridoma. These CTLs produce β-galactosidase upon recognition of the ovalbumin class I antigenic epitope SIINFEKL complexed with the MHC class I molecule H-2Kb, present on RAW 309.1 CR macrophages. Therefore, a measure of β-galactosidase activity can be used to determine the degree to which delivered ovalbumin is presented as a class I antigen. All tissue culture reagents were purchased from Invitrogen Corp, Carlsbad, Calif., unless otherwise noted. RAW 309.1 CR macrophages (ATCC, Manassas, Va.) were cultured in 90% DMEM with D-Glucose and L-glutamine, 10% fetal bovine serum (FBS), supplemented with 100 U/ml penicillin/100 μg/ml streptomycin. B3Z CTLs were a gift from Dr. Nilabh Shastri, UC Berkeley. They were cultured in 90% RPMI medium ...
Helper T cells are stimulated to fight infections or diseases upon recognition of peptides from antigens that are processed and presented by the proteins of Major Histocompatibility Complex (MHC) Class II molecules. Degradation of a full protein into small peptide fragments is a lengthy process consisting of many steps and chaperones. Malfunctions during any step of antigen processing could lead to the development of self-reactive T cells or defective immune response to pathogens. Although much has been accomplished regarding how antigens are processed and presented to T cells, many questions still remain unanswered, preventing the design of therapeutics for direct intervention with antigen processing. Here, we review published work on the discovery and function of a MHC class II molecular chaperone, HLA-DO, in human, and its mouse analog H2-O, herein called DO. While DO was originally discovered decades ago, elucidating its function has proven challenging. DO was discovered in association with
Accurate prediction of antigen presentation by human leukocyte antigen (HLA) class II molecules would be valuable for vaccine development and cancer immunotherapies. Current computational methods trained on in vitro binding data are limited by insufficient training data and algorithmic constraints. Here we describe MARIA (major histocompatibility complex analysis with recurrent integrated architecture; https://maria.stanford.edu/ ), a multimodal recurrent neural network for predicting the likelihood of antigen presentation from a gene of interest in the context of specific HLA class II alleles. In addition to in vitro binding measurements, MARIA is trained on peptide HLA ligand sequences identified by mass spectrometry, expression levels of antigen genes and protease cleavage signatures. Because it leverages these diverse training data and our improved machine learning framework, MARIA (area under the curve = 0.89-0.92) outperformed existing methods
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We applied doses between 1-25 Gy, which is lower or comparable with doses received by patients, and observed that ionizing radiation induces a dose-dependent increase in MHC class I presentation in two phases (Fig. 6). The first phase represents peptides derived from existing proteins, because inhibition of translation does not affect the generation of these peptides. More polyubiquitinated proteins for proteasomal degradation are observed swiftly after radiation even at doses of 1-4 Gy, resulting in more peptides for MHC class I antigen presentation and enhanced MHC class I expression as peptides are the limiting step in complex formation (37). Irradiation will result in the formation of free radicals even at low doses, and proteins will be modified directly by radiation or indirectly by radicals formed after water radiolysis, resulting in oxidation of various amino acids. These modifications may target the affected proteins for rapid degradation by the proteasome. Although this will reflect a ...
The importance of antiviral CD8+ T cell recognition of alternative reading frame (ARF)-derived peptides is uncertain. In this study, we describe an epitope (NS1-ARF21-8) present in a predicted 14-residue peptide encoded by the +1 register of NS1 mRNA in the influenza A virus (IAV). NS1-ARF21-8 elicits a robust, highly functional CD8+ T cell response in IAV-infected BALB/c mice. NS1-ARF21-8 is presented from unspliced NS mRNA, likely from downstream initiation on a Met residue that comprises the P1 position of NS1-ARF21-8 Derived from a 14-residue peptide with no apparent biological function and negligible impacts on IAV infection, infectivity, and pathogenicity, NS1-ARF21-8 provides a clear demonstration of how immunosurveillance exploits natural errors in protein translation to provide antiviral immunity. We further show that IAV infection enhances a model cellular ARF translation, which potentially has important implications for virus-induced autoimmunity ...
Herpes simplex virus type 1 (HSV-1) viral proteins are usually processed by the major histocompatibility complex (MHC) class I presentation pathway. This occurs after autophagy has facilitated this process. A second pathway is triggered later during infection. A recent study suggests a complex inter...
The invariant chain (Ii) binds nascent major histocompatibility complex (MHC) class II molecules, blocking peptide binding until the complex dissociates in the endosomes. This may serve to differentiate the MHC class I and II antigen presentation pathways and enable class II molecules to efficiently bind peptides in the endosomes. This hypothesis was addressed by probing spleen cells from a combination of knock-out and transgenic mice with a large panel of T cell hybridomas. The Ii molecule blocked the presentation of a range of endogenously synthesized epitopes, but some epitopes actually required Ii. Thus, the influence of Ii on presentation does not follow simple rules. In addition, mice expressing Ii were not tolerant to epitopes unmasked in its absence, a finding with possible implications for autoimmunity. ...
Antigen processing is an immunological process that prepares antigens for presentation to special cells of the immune system called T lymphocytes. It is considered to be a stage of antigen presentation pathways. This process involves two distinct pathways for processing of antigens from an organisms own (self) proteins or intracellular pathogens (e.g. viruses), or from phagocytosed pathogens (e.g. bacteria); subsequent presentation of these antigens on class I or class II major histocompatibility complex (MHC) molecules is dependent on which pathway is used. Both MHC class I and II are required to bind antigen before they are stably expressed on a cell surface. MHC I antigen presentation typically (considering cross-presentation) involves the endogenous pathway of antigen processing, and MHC II antigen presentation involves the exogenous pathway of antigen processing. Cross-presentation involves parts of the exogenous and the endogenous pathways but ultimately involves the latter portion of the ...
Antigen presentation is a key rate-limiting step in the immune response. Dendritic cells (DC) are the most potent antigen-presenting cells for naive T cells, due to their high expression of MHC and co-stimulatory molecules, but little is known about the biochemical pathways that regulate this function. We here demonstrate that monocyte-derived mature DC can be infected with adenovirus at high efficiency (|95%) and that this procedure can be used to dissect out which pathways are essential for inducing DC antigen presentation to naive T cells. Using adenoviral transfer of the endogenous inhibitor of NF-kappaB, IkappaBalpha, we show that DC antigen presentation is NF-kappaB dependent. The mechanism for this is that NF-kappaB is essential for three aspects of antigen-presenting function: blocking NF-kappaB coordinately down-regulates HLA class II, co-stimulatory molecules like CD80, CD86 and CD40, and immuno-stimulatory cytokines like IL-12 and tumor necrosis factor-alpha. In contrast adhesion molecules
Sage AP, Nus M, Murphy D, Finigan A, Baker L, Masters L and Mallat Z. Regulatory B cell specific interleukin-10 does not regulate atherosclerosis in mice. ATVB. 35(8):1770-3. doi: 10.1161/ATVBAHA.115.305568. Sage A, Murphy D, Sabir S, Grazia G, Maffia P, Masters L, Baker L, Finigan A, Harrison J, Ludewig B, Reith W, Hansson G, Reizis B, Hugues S, Mallat Z. (2014) MHC class II-restricted antigen presentation by plasmacytoid dendritic cells drives pro-atherogenic immunity. 14;130(16):1363-73. doi: 10.1161/CIRCULATIONAHA.114.011090.. Sage AP & Mallat Z. (2014). Multiple potential roles for B cells in atherosclerosis. Ann Med. doi:10.3109/07853890.2014.900272. Ait-Oufella H, Sage AP, Mallat Z, Tedgui A. (2014). Adaptive (T and B cells) immunity and control by dendritic cells in atherosclerosis. Circ Res, 114(10), 1640-1660. doi:10.1161/CIRCRESAHA.114.302761. Zouggari Y, Ait-Oufella H, Bonnin P, Simon T, Sage A, Guérin C, Vilar J, Caligiuri G, Tsiantoulas D, Laurans L, Dumeau E, Kotti S, Bruneval P, ...
Squamous cell carcinoma of the head and neck (SCCHN) cells can escape recognition and lysis by tumor antigen (TA)-specific cytotoxic T lymphocytes (CTL) by downregulation of antigen processing machinery (APM) components, such as the transporter associated with antigen processing (TAP)-1/2 heterodimer. APM component upregulation by interferon gamma (IFN-g) restores SCCHN cell susceptibility to lysis by CTL, but the mechanism underlying TAP1/2 downregulation in SCCHN cells is not known. Because IFN-g activates signal transducer and activator of transcription (STAT)-1, we investigated phosphorylated (p)-STAT1 as a mediator of low basal TAP1/2 expression in SCCHN cells. SCCHN cells were found to express basal total STAT1 but low to undetectable levels of pSTAT1. The association of increased pSTAT1 levels and APM components likely reflects a cause-effect relationship, since STAT1 knockdown significantly reduced both IFN-g-mediated APM component expression and TA-specific CTL recognition of IFN-g ...
IFN-producing killer dendritic cells (IKDC) represent a recently discovered cell type in the immune system that possesses a number of functions contributing to innate and adaptive immunity, including production of type 1and 2 IFNs, interleukin (IL)-12, natural killing, and ultimately antigen presentation to naïve T cells. Here, we compared in vitro and in vivo responses of mouse IKDC, conventional dendritic cells (DC), and natural killer (NK) cells to murine cytomegalovirus infection and found distinct functions among these cell subsets. Upon recognition of infected fibroblasts, IKDC, as well as NK, produced high level of IFN-γ, but unlike NK, IKDC simultaneously produced IL-12p40 and up-regulated MHC class II (MHC-II) and costimulatory molecules. Using MHC-II molecule expression as a phenotypic marker to distinguish activated IKDC from activated NK, we further showed that highly purified MHC-II+ IKDC but not NK cross-present MHC class I-restricted antigens derived from MCMV-infected targets ...
DCs are bone marrow-derived APCs that express high levels of MHC, adhesion molecules, and other important costimulatory molecules required for antigen presentation (32 , 33) . Their ability to take-up antigens and induce antigen-specific immunity has stimulated considerable interest in using them to treat cancer. However, naturally occurring DCs are exceptionally rare, comprising only 0.01-0.5% of circulating and tumor-infiltrating mononuclear leukocytes (19 , 34) . Even when present, DCs harvested from cancer patients often fail to express normal levels of antigen-presenting molecules and lack the ability to stimulate effective immune responses (27 , 34 , 35) . Enk et al. (35) purified CD83+ DCs from the tumors of patients with both regressing and progressing melanoma metastases. Whereas the DCs from regressing metastases expressed CD86 and functioned as APCs, the DCs recovered from progressing metastases expressed little CD86 and induced T-cell anergy instead of stimulation. Similarly, ...
Dendritic cells have the ability to control the balance between immunity and tolerance. Upon viral exposure, Dendritic Cells (DCs) steadily detect pathogens and exert their antigen presentation function to induce adaptive ...
Antigen presented to CD4+ T cells by major histocompatibility complex class II molecules (MHCII) plays a key role in adaptive immunity. Antigen presentation is initiated by the proteolytic cleavage of pathogenic or self proteins and loading of resultant peptides to MHCII. The loading and exchange of peptides to MHCII is catalyzed by a nonclassical MHCII molecule, HLA-DM (DM). It is well established that DM promotes peptide exchange in vitro and in vivo. However, the mechanism of DM-catalyzed peptide association and dissociation, and how this would affect epitope selection in human responses to infectious disease remain unclear. The work presented in this thesis was directed towards the understanding of mechanism of DM-mediated peptide exchange and its role in epitope selection. In Chapter II, I measured the binding affinity, intrinsic dissociation half-life and DM-mediated dissociation half-life for a large set of peptides derived from vaccinia virus and compared these properties to the peptide-specific
Cytotoxic T cells (also known as Tc, killer T cell, or cytotoxic T-lymphocyte (CTL)) express CD8 coreceptor are a population of T cells that are specialised for inducing programmed cell death of other cells. Cytotoxic T cells regularly patrol all body cells to maintain the organismal homeostasis. Whenever they encounter signs of disease, caused for example by the presence of viruses or intracellular bacteria or a transformed tumor cell, they initiate processes to destroy the potentially harmful cell.[1] All nucleated cells in the body (along with platelets) display class I major histocompatibility complex (MHC-I molecules). Antigens generated endogenously within these cells are bound to MHC-I molecules and presented on the cell surface. This antigen presentation pathway enables the immune system to detect transformed or infected cells displaying peptides from modified-self (mutated) or foreign proteins.[4][5]. In the presentation process, these proteins are mainly degraded into small peptides by ...
Tetanus toxin has been a valuable model antigen to study the MHC class II-restricted antigen processing pathway and is also frequently used to provide T helper determinants in vaccine formulations. To date most basic studies on the processing of this antigen have utilized human T and B cell clones. As a first step towards extending studies on this antigen into the murine system we have generated a panel of T cell clones and mAb in H-2b and H-2d mice. We investigated the presentation of tetanus toxin C fragment (TTCF) by the murine B cell lines LB27.4 (H-2dxb), A20 (H-2d) and IIA1.6 (H-2d) and the extent to which this could be modulated by the addition of mAb. One mAb, 10G5, induced strikingly enhanced presentation of T cell determinants located in the N-terminal region of TTCF while other antibodies inhibited presentation of these and other epitopes. The enhancing effects of the 10G5 antibody were blocked by the anti-FcR antibody 2.4G2 and were not observed in the FcR-negative IIA1.6 cell line. ...
HER-2/neu overexpression in tumor cells caused abnormalities of MHC class I surface expression due to impaired expression of components of the antigen-processing machinery (APM) including the low molecular weight proteins, the transporter associated
Introduction: Neutrophil elastase (NE) is an inflammatory mediator that is taken up by breast cancer cells. We have previously shown that NE uptake increases susceptibility to lysis by cytotoxic T lymphocytes (CTL) targeting the tumor antigens PR1 and cyclin E. We investigated whether NE uptake alters adaptive immunity by affecting MHC class I antigen presentation and T cell inhibitory molecules.. Methods: MDA-MB-231 breast cancer cells were maintained in standard media ± NE. Healthy donor HLA-A2+ peripheral blood mononuclear cells were used to generate antigen specific CTL by pulsing dendritic cells with E75, a HER2-derived epitope we are currently investigating as a vaccine in clinical trials. Calcein-AM cytotoxicity assays evaluated E75-specific lysis. Flow cytometry was used to show NE uptake, HLA-A2, pan-HLA class I (HLA-ABC) and PD-L1 surface expression. Western blot analysis was used to show total MHC class I heavy chain, B2M, LMP2, TAP1, calnexin and tapasin expression. Relative PD-L1 ...
TY - JOUR. T1 - DNAJC17 is localized in nuclear speckles and interacts with splicing machinery components. AU - Pascarella, A.. AU - Ferrandino, G.. AU - Credendino, S. C.. AU - Moccia, C.. AU - DAngelo, F.. AU - Miranda, B.. AU - DAmbrosio, C.. AU - Bielli, P.. AU - Spadaro, O.. AU - Ceccarelli, M.. AU - Scaloni, A.. AU - Sette, C.. AU - De Felice, M.. AU - De Vita, G.. AU - Amendola, E.. PY - 2018/12/1. Y1 - 2018/12/1. N2 - DNAJC17 is a heat shock protein (HSP40) family member, identified in mouse as susceptibility gene for congenital hypothyroidism. DNAJC17 knockout mouse embryos die prior to implantation. In humans, germline homozygous mutations in DNAJC17 have been found in syndromic retinal dystrophy patients, while heterozygous mutations represent candidate pathogenic events for myeloproliferative disorders. Despite widespread expression and involvement in human diseases, DNAJC17 function is still poorly understood. Herein, we have investigated its function through high-throughput ...
Precision machinerycomponents such as a cylinder in a magnetic tape scanning apparatus, a cylinder base and/or a sub-chassis in a video tape recorder, etc. made of cured thermosetting resin composition comprising (A) a resin component comprising, particularly preferably, a terephthalic acid series unsaturated polyester resin, styrene and a saturated polyester resin, (B) an inorganic filler, and (C) short fibrous material such as carbon short fibers, have excellent dimensional accuracy and dimensional stability. When these precision machinery components are used, for example, in a video tape recorder, the same clear VTR picture as in the case of using those made of metal can be obtained.
DRA_HUMAN] Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II ...
DPA1_HUMAN] Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II ...
FUNCTION: Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II ...
Cytomegaloviruses (CMVs) are expert evaders of nearly every aspect of our immune system. One of these strategies is the downregulation of surface MHC I molecules (major histocompatibility molecules class I). As MHC I molecules present peptides (small fragments) of all proteins generated within the cells to cytotoxic T cells, downregulation of MHC I molecules is an effective way of hiding a viral presence inside the cell from T cells.. Natural killer (NK) cells, lymphocytes that belong to innate immune systems, possess receptors called Ly49 in mice or KIR in humans. These receptors recognize MHC I molecules on the cell surface and inhibit the NK cell, preventing it from uncontrolled killing of cells. The NK cell is thus said to recognize "self" molecules. When MHC I molecules are downregulated upon virus infection, the NK cell is no longer inhibited by KIR or Ly49 receptors. In particular, when there are other activating signals or inflammation, the NK cell will kill the infected cell with ...
Antigen presentation describes a vital immune process which is essential for T cell immune response triggering. Because T cells recognise only fragmented antigens displayed on cell surfaces, antigen processing must occur before the antigen fragment, now bound to the major histocompatibility complex (MHC), is transported to the surface of the cell, a process known as presentation, where it can be recognized by a T cell receptor. If there has been an infection with viruses or bacteria, the cell will present an endogenous or exogenous peptide fragment derived from the antigen bound to MHC molecules. There are two types of MHC molecules which differ in the source of the antigens: MHC class I molecules (MHC-I) bind peptides from the cell cytosol, while peptides generated in the endocytic vesicles after internalisation are bound to MHC class II (MHC-II). Cellular membranes separate these two cellular environments - intracellular and extracellular. Each T cell can finally recognise only ten to hundreds ...
phdthesis{8ca468b5-f493-4f6c-aec3-d8b2f8e7dafd, abstract = {Type II collagen (CII) is the main protein component of cartilage and immune recognition of CII plays a critical role for the development of collagen induced arthritis (CIA), a widely used animal model for rheumatoid arthritis (RA).,br/,,br, ,br/,,br, Antigen presentation is an important requirement for the immune response, the more efficient presentation of the antigen the better tolerance will be induced and thereby protect against arthritis. Out of different professional antigen presenting cells (APCs), Langerhans cells (LCs), a subtype of dendritic cells, have been shown to poorly present CII compared to other antigens tested, but also compared to other APCs like B cells and macrophages. The inability to present CII is an exception from the rule that dendritic cells (DCs) are efficient in antigen presentation and subsequently in priming of naive T cells. This incompetence could however be overcome by treating with cysteine protease ...
MHC II molecules are transmembrane heterodimeric glycoproteins that play a key role in the immune response cascade. MHC II molecules are expressed exclusively in antigen presenting cells (APC). The primary function of APCs are to ingest, process, and present protein antigens to T-cells to initiate humoral immune response. In this process antigens enter APCs via phagocytosis or endocytosis. Once in the cell they are proteolyzed by endosomes and subsequently bound by MHC II molecules. MHC II transports the antigenic peptide to the surface of the APC, where the peptide MHC II complex fuses to the receptors on CD4+ T-cells, initiating immune response to eliminate the antigen. Expression of MHC II molecules is regulated by a trans-acting multi-protein complex called the MHCII enhanceosome. The MHCII enhanceosome is comprised of four proteins RFX, NFY, CREB, and CIITA. RFX, NFY, and CREB are found in all somatic cells, however the interaction of these three proteins alone does not induce expression of ...
First described in 1973 by Ralf Steinman, dendritic cells have since attracted considerable attention. Their properties of antigen capture, presentation and T cell activation, place them both as a key bridge between the innate and adaptive immunity, as well as a switch between tolerance and immunity. Although, the human and mouse DC network share many similarities, one subset was discovered in mouse that had not yet found its equivalent in human: the CD8+ DC characterised by their ability produce IL-12, but most particularly to uptake dead cells and "cross-present" these exogenous antigens on MHC class I molecules. This function has been shown to be essential in the immune defense against many viruses, intracellular bacteria and tumors as well as for the maintenance of self tolerance. Four studies in J. Exp. Med provide insight into a potential human homologue to the mouse cross-presentation specialist CD8+ DC. A nice minireview from two DC experts: Villadangos and Shortman. ...
PRESENTATION PREFERENCES. Each submitter will be able to choose an abstract type among three categories:. Oral: "Full oral" presentations are 7 minutes long (5 minutes for presentation, 2 minutes Q&As) and "Brief oral" presentations are 3 minutes long (2 minutes for presentation, 1 minutes Q&As). Poster: Posters for ESOT 2017 will be accepted and presented as ePosters ONLY. A digital version of the poster will be required after you have received a notification of acceptance of your abstract. You can download a template for this submission from the Abstracts tab of the platform.. Video: Abstracts selected for video presentations will be evaluated separately and submitters will be informed of its acceptance in time for the full video to be presented and evaluated.. Guidelines for Video submission: ...
May 4, 2010 - PACT Web Seminar. The NHLBI and EMMES (PACT Coordinating Center) presentations are available for viewing and printing using the link below. The 5 PACT facility speaker presentations are not available on our website. Please contact the speakers regarding their presentations. Speaker contact information can be found in the Webcast Overview Document embedded in the link below:. May 4, 2010 PACT Webcast Presentation Overview ...
Unlike B cells, CD8-positive and CD4-positive T cells of the adaptive immune system do not recognize intact foreign proteins but instead recognize polypeptide fragments of potential antigens. These antigenic peptides are expressed on the surface of antigen presenting cells bound to MHC class I and MHC class II proteins. Here, we review the basics of antigen acquisition by antigen presenting cells, antigen proteolysis into polypeptide fragments, antigenic peptide binding to MHC proteins, and surface display of both MHC class I-peptide and MHC class II-peptide complexes.
Major histocompatibility complex class II (MHC-II) molecules are expressed on the surface of professional antigen-presenting cells where they display peptides to T helper cells, which orchestrate the onset and outcome of many host immune responses. Understanding which peptides will be presented by the MHC-II molecule is therefore important for understanding the activation of T helper cells and can be used to identify T-cell epitopes. We here present updated versions of two MHC-II-peptide binding affinity prediction methods, NetMHCII and NetMHCIIpan. These were constructed using an extended data set of quantitative MHC-peptide binding affinity data obtained from the Immune Epitope Database covering HLA-DR, HLA-DQ, HLA-DP and H-2 mouse molecules. We show that training with this extended data set improved the performance for peptide binding predictions for both methods. Both methods are publicly available at www.cbs.dtu.dk/services/NetMHCII-2.3 and www.cbs.dtu.dk/services/NetMHCIIpan-3.2. PMID: ...
It is generally accepted that antigens in the cytoplasm are loaded in the endoplasmic reticulum and presented at the cell surface on major histocompatibility complex (MHC) class I molecules, whereas peptides present in endo/phagocytic compartments are presented on MHC class II molecules ...
Clone REA230 recognizes a monomorphic epitope on MHC class I molecules, HLA A, B, and C. MHC class I molecules are expressed by all human nucleated cells and are involved in presentation of peptide ligands on the cell surface for recognition by cytotoxic T cells. Additional information: Clone REA230 displays negligible binding to Fc receptors. - USA
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Amit Bar-Or, MD, FRCPC Neuroimmunology Unit Montreal Neurological Institute Montreal, QC, Canada . B cells: Beyond Antibodies November 1 st , 2006. Outline. Antibody-independent roles of B cells antigen presentation (APC) innate immunity (environment/immune interface) Slideshow 141290 by oshin
A set of T cell clones (TCC) isolated from HLA-DR-, Dw-, DQ-matched allogeneic MLCs was found to proliferate autonomously when stimulated with cells carrying a wide range of class I or II specificities. This apparently unrestricted proliferation was relatively weak, and only low levels of IL-2 were present in the supernatants of stimulated cells. Autologous as well as allogeneic PBMC and B lymphoblastoid cell lines (B-LCL) were capable of stimulating such clones, which were also restimulated by suppressive, but not by helper, TCC. Moreover, such clones displayed the unusual property of autostimulation. mAb inhibition experiments suggested that class II- or class II-restricted antigens were involved in stimulation. Thus, certain "broad" mAbs (TU39, SG520) reacting with multiple locus products inhibited activation of these reagents, but none of those reacting more specifically with DR (TU34, TU37, L243, Q2/70, SG157), DQ (TU22, SPV-L3, Leu 10), or DP (B7/21), or mixtures of these mAbs, were able ...
Taken together, these results may explain the paradox of why removal of the GAr sequence from EBNA1 has only a limited effect on EBNA1 expression in cells. Apparently, the increase in synthesis of EBNA1 after removal of GAr is almost completely compensated for by the subsequent increase in the rate of degradation. The idea that GAr-mediated inhibition of proteasomal degradation of full-length EBNA1 is sufficient to avoid EBNA1-derived peptides from being processed and loaded onto MHC class I molecules (9, 11) is not in accordance with the DRiP hypothesis (13, 14, 20). We therefore tested directly whether the inhibition of proteasomal degradation was sufficient to protect GAr chimeric proteins from being processed and presented on MHC class I molecules. To do this, we took advantage of the fact that GAr-mediated self-inhibition of mRNA translation is dependent on the location of GAr within the protein, whereas inhibition of proteasomal degradation is not (Fig. 3, A and B) (11). Thus, by changing ...
Hi, Yes, some medications can have effects on interleukins, but this amount of down regulation of antigen presentation is quite minimal and will not affect HIV antibody tests. The immune system is...
The most common reasons that business presentations are usually so awful, along with advice to make your presentations better.
This is a quick gallery of photos to go through about problems with presentations. I love that the diagnosis of the problem, along with tips for avoiding it, are included with each image. Just click on the first image to cycle through the gallery.

The core message? Without a coherent story, your presentation will fail. So take these tips to heart. | Just Story It
PREREQUISITE: A100 and A150 or permission of instructor CLASS PRESENTATIONS: Special presentations will be made throughout the course related to a particular "grammar focus". These presentations will be graded based on creativity, sign production, usage of non-manual modifiers/signals, contextual accuracy, fluency and comprehension. These presentations should be done with a minimum amount of fingerspelling. Lesson presentations are graded on a scale of 1-100. If your lesson is not presented on the date assigned, the grade is lowered by 10 points. Presentations must be reviewed by an AI at least one week prior to the assigned presentation date. Check the AI office door (SG C101) for your presentation deadline date. Two points will be deducted from the presentation grade for each day past the deadline date if it has not been reviewed with an AI. SPECIAL PROJECT: A special project will be due. You must participate in three out-of-class activities involving Deaf culture, and interact with a Deaf ...
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Abdominal radiology presentations are a relatively distinct group of presentations that precipitate assessment medical and surgical teams.
Protein antigens are no able to induce an immune response without being previously processed by antigen presenting cells (APCs). Following their processing that comprises their splitting to smaller fragments - peptides, APs subsequently present them to T cells; moreover, they activate them and polarise to a specific biological functions. Depending of antigen origin, there are two presentation pathways, exogenous and endogenous. Antigens originated from outside of APC, e.g. bacterial toxins, enzymes, etc., are presented by exogenous pathway and presented molecules are class II HLA molecules. T cell, that recognise presented peptides belong to helper subset of T cells. Antigens originated in the cytosol, such as antigens that appear in the cytoplasm of virus infected cells, are presented by endogenous pathway and presented molecules belong to class I HL-A molecules. T cells, that recognise presented peptides, represent cytotoxic T cells.
These presentations are classified and categorized, so you will always find everything clearly laid out and in context. We are staying up to date! We are looking for more relevant data on social networks. 2014 SlideSearchEngine.com Contact ...
These presentations are classified and categorized, so you will always find everything clearly laid out and in context. We are staying up to date! We are looking for more relevant data on social networks. 2014 SlideSearchEngine.com Contact ...
I have worked in the field of persistent pain for 8 years, I am continuously challenged. I get stuck and frozen by the complexity of presentations, because no two presentations are the same, despite the fact that those two very different presentations have a referral for the same pain problem (back pain for example). People experience…
Their evaluation is based on two types of participation: Each student makes a formal presentation of his or her research to other members of the Oukka laboratory no less than once per quarter. Presentations are expected to consist of background (including a brief review of the relevant literature), research goals and hypotheses, research results (both recent and cumulative), summary of the findings, interim conclusions, and discussion of plans for the future. The student must respond to questions and critiques by Dr. Oukka, post-doctoral fellows, and other students in the laboratory. Recommended preparation ...
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Environmental danger cues trigger DC maturation and stimulate DCs for enhanced antigen presentation and production of polarizing cytokines, which drive T cells to acquire effector function. The coincidence of DC maturation and immunogenic function in this context has been interpreted to signify that DC maturation and functional status are mechanistically linked binary states, i.e., immature DCs are tolerogenic whereas mature DCs are immunogenic. However, this simple model does not sufficiently capture the spectrum of DC function in tolerance or immunity. Steady-state MigDCs that promote tolerance express high levels of MHCII and costimulatory molecules and do not provoke autoimmune responses (Ruedl et al., 2000). Furthermore, different classes of pathogens can elicit distinctive transcriptional responses in DCs that lead to priming of varied Teff states (Huang et al., 2001; Garber et al., 2012) . This suggests that distinct cues can stimulate DCs to adopt divergent mature states specialized to ...
frequently however, multiple nerves are affected, called polyneuropathy. An increasingly common nutrition allergic presentation are oral symptoms such as itching herpes swelling of the mouth and throat obstruction with respiratory difficulties. Mine is caused by the allergies and even a strong antihistamine prescribed by doctor isnt helping and I think is making it worse. She will leak fluids and tissues, called lochia, for several weeks after giving birth. The welts can drive you crazy and patients can also have swelling of lips, eyes, hands or feet - swellings which can be dramatic. This extra fluid the tissues causes swelling and itchiness. What do you think he meant by, Thats the -term future: vaccination and no screening?. Our department is nationally recognized for its expertise in the diagnosis and treatment of skin disorders and skin cancer. 15 Nov 2007 Several months ago I went to the doctor with hives all over my body. CFIDS patients typically have very high viral titers. Is this ...
Type 1 Diabetes is an autoimmune condition in which segments of the immune system cause the destruction of insulin producing cells in the pancreas, leaving individuals with an impaired ability to control blood glucose levels. Currently there is no cure for Type 1 Diabetes and the treatments involve lifelong insulin administration and careful monitoring of blood glucose levels. Long-term complications like cardiovascular disease, nerve damage, and retina damage, may result. Previous studies have shown that improvement in the control of blood glucose can reduce the risks from these long-term complications. Residual insulin production, typically within the first few years following diagnosis, helps to reduce an individuals need to supplement insulin by injection or pump. This effect helps in maintaining the bodys ability to regulate blood glucose levels and reducing the needs of external insulin.. Methyldopa, or Aldomet, has been approved by the Food and Drug Administration and is commonly used ...
Among other features, peptides affect MHC class II molecules, causing changes in the binding of bacterial superantigens (b-Sag). Whether peptides can alter binding of viral superantigens (v-Sag) to MHC class II was not known. Here we addressed the question of whether mutations limiting the diversity of peptides bound by the MHC class II molecules influenced the presentation of v-Sag and, subsequently, the life cycle of the mouse mammary tumor virus (MMTV). T cells reactive to v-Sag were found in mice lacking DM molecules as well as in A(b)Ep-transgenic mice in which MHC class II binding grooves were predominantly occupied by an invariant chain fragment or Ealpha(52-68) peptide, respectively. APCs from the mutant mice failed to present v-Sag, as determined by the lack of Sag-specific T cell activation, Sag-induced T cell deletion, and by the aborted MMTV infection. In contrast, mice that express I-A(b) with a variety of bound peptides presented v-Sag and were susceptible to MMTV infection.
Human cytomegalovirus encodes two glycoproteins, US2 and US11, which cause rapid degradation of MHC class I molecules, thus preventing recognition of virus-infected cells by the immune system. This degradation process involves retrograde transport or dislocation of MHC class I molecules from the endoplasmic reticulum (ER) to the cytosol, where they are deglycosylated by an N-glycanase and degraded by the proteasome. At present it is unknown whether ubiquitination is required for US2- and US11-mediated dislocation and degradation of MHC class I molecules. Here, we show that in E36ts20 hamster cells, which contain a temperature-sensitive mutation in the E1 ubiquitin-activating enzyme, US11-mediated degradation of MHC class I molecules is strongly impaired at the non-permissive temperature, indicating the necessity for ubiquitination in this process. We next addressed the question of whether ubiquitination is a condition for the retrograde movement of MHC class I molecules from the ER to the ...
We have analyzed peptides associated with six human major histocompatibility complex (MHC) class I allomorphs expressed by the U937 cell line. Peptides were isolated by mild acid elution or by MHC class I immunoprecipitation by using W6/32 monoclonal antibody. Eighty-five peptides were sequenced by mass spectrometry, and their putative binding alleles were assigned using bioinformatic tools. Only three peptides isolated by the two approaches were identical, suggesting that the approaches may yield distinct partially overlapping peptide populations. Mild acid treatment-derived peptides manifested overall characteristics suggestive of relatively lower affinity of binding for MHC class I. Interestingly, a large proportion of putative HLA-B*5101-binding peptides was evident among the mild acid treatment-eluted peptides, and to a lesser degree in the affinity-purified peptide pool. These results suggest that HLA-B*5101 may bind a potentially large pool of peptides with relatively lower affinity. We suggest
Vaccinia virus (VV) inhibits the presentation of certain epitopes from influenza virus nucleoprotein (NP), haemagglutinin (HA) and non-structural 1 (NS1) proteins to CD8+ cytotoxic T lymphocytes (CTL) by an unknown mechanism. We have investigated whether VV genes B13R and B22R, which encode proteins with amino acid similarity to serine protease inhibitors (serpins), are involved in this process. Recombinant VVs were constructed which express influenza virus proteins HA, NP or NS1 and which lack serpin gene B13R or both B13R and B22R. The lysis of cells infected with these viruses by influenza virus-specific CD8+ CTL was compared to the lysis of cells infected with viruses expressing both the influenza proteins and the serpin genes. Cytotoxicity assays showed that deletion of the VV serpin genes B13R and B22R and other genes between B13R and B24R did not increase the level of lysis, indicating that these genes are not involved in inhibition of antigen presentation of the epitopes tested.
Background: The major histocompatibility complex (MHC) is responsible for presenting antigens (epitopes) on the surface of antigen-presenting cells (APCs). When pathogen-derived epitopes are presented by MHC class II on an APC surface, T cells may be able to trigger an specific immune response. Prediction of MHC-II epitopes is particularly challenging because the open binding cleft of the MHC-II molecule allows epitopes to bind beyond the peptide binding groove; therefore, the molecule is capable of accommodating peptides of variable length. Among the methods proposed to predict MHC-II epitopes, artificial neural networks (ANNs) and support vector machines (SVMs) are the most effective methods. We propose a novel classification algorithm to predict MHC-II called sparse representation via 1-minimization. Results: We obtained a collection of experimentally confirmed MHC-II epitopes from the Immune Epitope Database and Analysis Resource (IEDB) and applied our 1-minimization algorithm. To benchmark the
Although HLA class II molecules are well recognized to present peptide antigens to T cells, recently we found that ER misfolded proteins are transported to the cell surface by HLA class II molecules when they are associated with the peptide-binding groove of HLA class II molecules.32 Furthermore, intact IgG heavy chain is transported to the cell surface by HLA class II molecules via association with the peptide-binding groove, and IgG heavy chain/HLA class II complexes are recognized by autoantibodies in rheumatoid factor-positive sera from RA patients.33 In contrast, autoantibodies in rheumatoid factor-positive sera from non-RA individuals did not bind to IgG heavy chain/HLA class II complexes, suggesting that IgG heavy chain complexed with HLA-DR is a specific target for autoantibodies from RA patients. Of note, a strong correlation between autoantibody binding to IgG complexed with certain HLA-DR alleles and the odds ratio for association of these alleles with RA was observed.33 These ...

Prolonging Antigen Presentation | Science SignalingProlonging Antigen Presentation | Science Signaling

Thus, whereas macrophages rapidly degrade the antigens they encounter, dendritic cells may protect the very same antigens, ... Differential lysosomal proteolysis in antigen-presenting cells determines antigen fate. Science 307, 1630-1634 (2005). [ ... However, Delamarre et al. now find that the most efficient of the antigen-presenting cells (dendritic cells and B cells) harbor ... It has been assumed that antigen-presenting cells must have exceptionally well developed capacities for proteolysis because ...
more infohttp://stke.sciencemag.org/content/2005/275/tw101

Antigen PresentationAntigen Presentation

HLA-I Antigen Presentation and Tapasin Influence Immune Responses Against Malignant Brain Tumors - Considerations for ... HLA class I is most tightly linked to levels of tapasin compared with other antigen-processing proteins in glioblastoma Thuring ... Tapasin and human leukocyte antigen class I dysregulation correlates with survival in glioblastoma multiforme. Thuring, Camilla ...
more infohttps://lup.lub.lu.se/search/organization/V1000352

Antigen Presentation & T/NK Cell ActivationAntigen Presentation & T/NK Cell Activation

We develop novel platforms for the in vitro diagnostics of tumor-antigen specific T cells (joint project with Dr. Z rnig/Prof. ...
more infohttps://www.dkfz.de/en/angewandte-tumor-immunitaet/Antigen-Presentation-and-T-NK-Cell-Activation/index.html?m=1528122060

Antigen presentation by keratinocytes directs autoimmune skin disease | PNASAntigen presentation by keratinocytes directs autoimmune skin disease | PNAS

Antigen presentation by keratinocytes directs autoimmune skin disease. Lian Fan, Brian W. Busser, Traci Q. Lifsted, David Lo, ... Antigen presentation by keratinocytes directs autoimmune skin disease. Lian Fan, Brian W. Busser, Traci Q. Lifsted, David Lo, ... Antigen presentation by keratinocytes directs autoimmune skin disease. Lian Fan, Brian W. Busser, Traci Q. Lifsted, David Lo, ... Antigen presentation by keratinocytes directs autoimmune skin disease Message Subject (Your Name) has sent you a message from ...
more infohttps://www.pnas.org/content/100/6/3386

Antigen presentation and T cell stimulation by dendritic cells.  - PubMed - NCBIAntigen presentation and T cell stimulation by dendritic cells. - PubMed - NCBI

Antigen presentation in dendritic cells is finely regulated: antigen uptake, intracellular transport and degradation, and the ... Antigen presentation and T cell stimulation by dendritic cells.. Guermonprez P1, Valladeau J, Zitvogel L, Théry C, Amigorena S. ... Dendritic cells take up antigens in peripheral tissues, process them into proteolytic peptides, and load these peptides onto ... Dendritic cells then migrate to secondary lymphoid organs and become competent to present antigens to T lymphocytes, thus ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/11861614?dopt=Abstract

Antigen presentation by monocytes and monocyte-derived cells.  - PubMed - NCBIAntigen presentation by monocytes and monocyte-derived cells. - PubMed - NCBI

Antigen presentation by monocytes and monocyte-derived cells.. Randolph GJ1, Jakubzick C, Qu C. ... Then we evaluate the role of monocytes in T-dependent immunity, considering their role in acquiring antigens for presentation ... In the bone marrow, they can take up antigens from at least some other neighboring cells, and these antigens can be presented ... Monocyte subsets, access to antigen, and possible relationships to DCs and antigen-presenting cells that drive T-independent ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/18160272?dopt=Abstract

Predicting HLA class II antigen presentation through integrated deep learning | Nature BiotechnologyPredicting HLA class II antigen presentation through integrated deep learning | Nature Biotechnology

... a multimodal recurrent neural network for predicting the likelihood of antigen presentation from a gene of interest in the ... A neural network trained on diverse datasets improves prediction of HLA class II epitope presentation. ... expression levels of antigen genes and protease cleavage signatures. Because it leverages these diverse training data and our ... Accurate prediction of antigen presentation by human leukocyte antigen (HLA) class II molecules would be valuable for vaccine ...
more infohttps://www.nature.com/articles/s41587-019-0280-2?error=cookies_not_supported&code=43bd4dd0-a883-4899-8729-4e150abe3839

Frontiers | The Role of FcRn in Antigen Presentation | ImmunologyFrontiers | The Role of FcRn in Antigen Presentation | Immunology

FcRn-mediated antigen presentation has important consequences in tissue compartments replete with IgG and serves not only to d ... FcRn-mediated antigen presentation has important consequences in tissue compartments replete with IgG and serves not only to ... Critically, FcRn-driven T cell priming is efficient at very low doses of antigen due to the exquisite sensitivity of the IgG- ... Critically, FcRn-driven T cell priming is efficient at very low doses of antigen due to the exquisite sensitivity of the IgG- ...
more infohttps://www.frontiersin.org/articles/10.3389/fimmu.2014.00408/full

The Role of HLA-DM in Class II Antigen Presentation | SpringerLinkThe Role of HLA-DM in Class II Antigen Presentation | SpringerLink

The presentation of antigen to T cells requires that the antigens first be processed prior to presentation. Peptide binding ... Coordinate defects in human histocompatibility leukocyte antigen class II expression and antigen presentation in bare ... Antigen presentation and assembly by mouse I-Ak class II molecules in human APC containing deleted or mutated HLA DM molecules ... Defective processing and presentation of exogenous antigens in mutants with normal HLA class II genes. Nature 1990; 343: 71-74. ...
more infohttps://link.springer.com/chapter/10.1007/978-1-4684-6462-7_7

Research Associate in Antigen Presentation - Kings College London - jobs.ac.ukResearch Associate in Antigen Presentation - King's College London - jobs.ac.uk

Research Associate in Antigen Presentation. Kings College London Sorry, but the advert you were looking for has expired. ...
more infohttp://www.jobs.ac.uk/job/BDX020/research-associate-in-antigen-presentation/

Genetic modulation of antigen presentation by HLA-B27 molecules. | JEMGenetic modulation of antigen presentation by HLA-B27 molecules. | JEM

Genetic modulation of antigen presentation by HLA-B27 molecules.. L Pazmany, S Rowland-Jones, S Huet, A Hill, J Sutton, R ... Genetic modulation of antigen presentation by HLA-B27 molecules.. L Pazmany, S Rowland-Jones, S Huet, A Hill, J Sutton, R ... These data are compatible with the presence of a factor(s), possibly HLA linked, interfering with antigen presentation by ... In studies of antigenic peptide presentation, we have found a healthy volunteer whose lymphoblastoid cells were unable to ...
more infohttp://jem.rupress.org/content/175/2/361

Professional Antigen-Presentation Function by Human γδ T Cells | ScienceProfessional Antigen-Presentation Function by Human γδ T Cells | Science

Professional Antigen-Presentation Function by Human γδ T Cells Message Subject. (Your Name) has forwarded a page to you from ... Thus, when activated, these cells efficiently processed and displayed antigens and provided co-stimulatory signals sufficient ... A subset of nonconventional T cells unexpectedly present foreign antigens and stimulate the human immune system. ... A subset of nonconventional T cells unexpectedly present foreign antigens and stimulate the human immune system. ...
more infohttps://science.sciencemag.org/content/309/5732/264

Mesoporous Silicon Microparticles Enhance MHC Class I Cross-Antigen Presentation by Human Dendritic CellsMesoporous Silicon Microparticles Enhance MHC Class I Cross-Antigen Presentation by Human Dendritic Cells

The aim of this work was to use MSMPs to deliver viral specific MHC class I restricted epitopes into human antigen presenting ... We show for the first time that MSMPs vehiculation of antigenic peptides enhances their MHC class I presentation by human MDDCs ... cells (monocyte derived dendritic cells, MDDCs) to facilitate their capture, processing, and presentation to CD8+ (cytotoxic) T ... Specific Antigen CTL Presentation Assay: IFN Gamma ELISPOT Assay. Antigen-specific CD8 T cells producing IFN gamma were ...
more infohttps://www.hindawi.com/journals/jir/2013/362163/

Glycolipid antigen presentation to CD1-restricted T cells | IPBSGlycolipid antigen presentation to CD1-restricted T cells | IPBS

Lipids are important antigens that induce T cell-mediated specific immune responses. They are presented to T cells by a class ... Altogether, lipid antigen properties make them attractive for their use in subunit vaccines against Mtb. ... Molecular mechanisms of lipid antigens processing: functional and structural studies of CD1e, definition of the repertoire of ... We previously described that some mycobacterial glycolipid antigens must be processed, however the underlying molecular ...
more infohttp://www.ipbs.fr/index.php/glycolipid-antigen-presentation-cd1-restricted-t-cells

Frontiers | Expanded Human Blood-Derived γδT Cells Display Potent Antigen-Presentation Functions | ImmunologyFrontiers | Expanded Human Blood-Derived γδT Cells Display Potent Antigen-Presentation Functions | Immunology

γδT-antigen-presenting cells (APC), activated γδT cells with antigen-presentation function, might be a valuable alternative to ... αβT cells via antigen cross-presentation, a process involving the uptake and proteasomal processing of exogenous antigen and ... Antigen-Presentation Assay. Intracellular IFNγ assay. Day 14 γδT cells from HLA-A2+ blood donors were incubated for 16-24 h in ... Antigen-Presentation by Expanded γδT Cells (γδT-APCs). The purpose of this study was to determine whether expanded γδT cells ...
more infohttps://www.frontiersin.org/articles/10.3389/fimmu.2014.00344/full

JCI -
Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune responseJCI - Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response

Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response. ... Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response. ... This synergy was dependent on TAA cross presentation to cytolytic CD8+ T cells and on IFN-γ. Notably, butyrate, a metabolite ... inducing tumor-associated antigen (TAA) cross-priming with antitumor CD8+ T cell elicitation and abscopal effects. We tested ...
more infohttps://www.jci.org/articles/view/124332/pdf

An Alternative Path for Antigen Presentation: Group 1 CD1 Proteins | The Journal of ImmunologyAn Alternative Path for Antigen Presentation: Group 1 CD1 Proteins | The Journal of Immunology

Evasion and subversion of antigen presentation by Mycobacterium tuberculosis. Tissue Antigens74: 189-204. ... Antigen presentation by CD1 molecules and the generation of lipid-specific T cell immunity. Cell. Mol. Life Sci.64: 1824-1840. ... Antigen presentation by CD1 lipids, T cells, and NKT cells in microbial immunity. Adv. Immunol.102: 1-94. ... An Alternative Path for Antigen Presentation: Group 1 CD1 Proteins Message Subject (Your Name) has forwarded a page to you from ...
more infohttp://www.jimmunol.org/content/184/7/3303

In Vivo Detection of Dendritic Cell Antigen Presentation to CD4+ T Cells | JEMIn Vivo Detection of Dendritic Cell Antigen Presentation to CD4+ T Cells | JEM

In Vivo Detection of Dendritic Cell Antigen Presentation to CD4+ T Cells. Elizabeth Ingulli, Anna Mondino, Alexander Khoruts, ... 1984) Antigen recognition by H-2-restricted T cells. II. A tryptic ovalbumin peptide that substitutes for processed antigen. J ... probably because all of the DC have access to antigen and are thus in competition with each other for antigen presentation to ... In Vivo Detection of Dendritic Cell Antigen Presentation to CD4+ T Cells ...
more infohttp://jem.rupress.org/content/185/12/2133?ijkey=65bf1e1f209e6993c9765e214d26734dbcd799cc&keytype2=tf_ipsecsha

Antigen presentation - WikipediaAntigen presentation - Wikipedia

... protein/protein interactions and more for genes involved in antigen processing and presentation antigen presentation at the US ... Because T cells recognise only fragmented antigens displayed on cell surfaces, antigen processing must occur before the antigen ... Cross-presentation is a special case in which MHC-I molecules are able to present extracellular antigens, usually displayed ... This antigen presentation pathway enables the immune system to detect transformed or infected cells displaying peptides from ...
more infohttps://en.wikipedia.org/wiki/Antigen_presentation

Analysis of Lymphocytic Choriomeningitis Virus Antigens Presentation by MacrophagesAnalysis of Lymphocytic Choriomeningitis Virus Antigens Presentation by Macrophages

The activation of cytotoxic T-cell (CTL) responses requires antigen presentation by professional antigen presenting cells. ... which adversely affected antigen cross-presentation due to potent and enhanced antigen degradation. ... that provide sufficient LCMV antigens after virus inactivation with no possible direct antigen presentation. Our results ... As a result of examining the antigen presentation of Sp-MØ during differentiation, we reported that Sp-MØ down-regulated their ...
more infohttps://qspace.library.queensu.ca/handle/1974/5529

Class II MHC Self-Antigen Presentation in Human B and T LymphocytesClass II MHC Self-Antigen Presentation in Human B and T Lymphocytes

... PLoS ONE 7(1): e29805. ... Class II MHC Self-Antigen Presentation in Human B and T Lymphocytes. ... but the endogenous peptide repertoire of these non-classical antigen presenting cells remains unknown. We eluted and sequenced ...
more infohttps://dash.harvard.edu/handle/1/10288453

Ethanol Inhibits Antigen Presentation by Dendritic Cells | Clinical and Vaccine ImmunologyEthanol Inhibits Antigen Presentation by Dendritic Cells | Clinical and Vaccine Immunology

Ethanol suppresses allogeneic antigen presentation.The inhibitory effect of ethanol on allogeneic peptide presentation by CD11c ... Ethanol does not impact cross-presentation of exogenous antigens.To determine the potential effects of ethanol on antigen cross ... It was observed that ethanol impairs not only allogeneic peptide presentation but also presentation of exogenous antigens by ... Ethanol Inhibits Antigen Presentation by Dendritic Cells Message Subject (Your Name) has forwarded a page to you from Clinical ...
more infohttps://cvi.asm.org/content/18/7/1157

Distinct Protease Requirements for Antigen Presentation In Vitro and In Vivo | The Journal of ImmunologyDistinct Protease Requirements for Antigen Presentation In Vitro and In Vivo | The Journal of Immunology

Antibody modulation of antigen presentation: positive and negative effects on presentation of the tetanus toxin antigen via the ... Distinct Protease Requirements for Antigen Presentation In Vitro and In Vivo. Stephen P. Matthews, Ingrid Werber, Jan Deussing ... Distinct Protease Requirements for Antigen Presentation In Vitro and In Vivo. Stephen P. Matthews, Ingrid Werber, Jan Deussing ... Distinct Protease Requirements for Antigen Presentation In Vitro and In Vivo Message Subject (Your Name) has forwarded a page ...
more infohttps://www.jimmunol.org/content/184/5/2423
  • Molecular mechanisms of lipid antigens processing: functional and structural studies of CD1e, definition of the repertoire of lipid-derived epitopes, characterization of lysosomal enzymatic activities involved in the generation of lipid epitopes. (ipbs.fr)
  • responses via cross-presentation, and characterized how different epitopes from LCMV are cross presented in vitro and in vivo. (queensu.ca)
  • In contrast, the elimination of cathepsin B did not affect the presentation of epitopes from OVA or HEL ( 6 ), and cathepsin L-deficient splenocytes presented a range of Ags normally ( 7 ). (jimmunol.org)
  • Although monomeric HEL efficiently engages the BCR, presentation of HEL-derived epitopes is impaired compared to oligovalent antigens. (pnas.org)
  • SIAT® antigen presentation assay service from Creative Biolabs is able to deliver this information about TCR epitopes through interpretation of what DCs naturally says. (creative-biolabs.com)
  • The functional relevance of the TCR epitopes identified by SIAT® antigen presentation assay can be confirmed by various other services of the SIAT® platform including in silico , in vitro, ex vivo , in vivo immunogenicity assessments. (creative-biolabs.com)
  • Whereas small soluble antigens can be taken up passively via macropinocytosis or fluid phase endocytosis, larger antigens require processes such as phagocytosis for cellular entry. (frontiersin.org)
  • As a result of examining the antigen presentation of Sp-MØ during differentiation, we reported that Sp-MØ down-regulated their ability to cross-present the cell-associated lymphocytic choriomeningitis virus nucleoprotein (LCMV-NP) but not the soluble OVA proteins without altering their capacity to directly present LCMV antigens after infection. (queensu.ca)
  • This trait may help explain the known ability of soluble, disaggregated antigen to induce a state of B cell tolerance. (pnas.org)
  • Accumulation of HLA-DM, a regulator of antigen presentation, in MHC class II compartments. (springer.com)
  • We explored the role of antigen valency in B cell receptor (BCR) activation and rearrangement of intracellular MHC class II compartments as factors that contribute to the efficacy of antigen presentation. (pnas.org)
  • Furthermore, oligovalent HEL induced more pronounced rearrangement of MHC class II-containing antigen-processing compartments. (pnas.org)
  • The observed increase in rearrangement of MHC class II-positive compartments and the disposition of antigen-bound BCRs therein correlates with improved presentation of a HEL-derived epitope. (pnas.org)
  • In addition to in vitro binding measurements, MARIA is trained on peptide HLA ligand sequences identified by mass spectrometry, expression levels of antigen genes and protease cleavage signatures. (nature.com)
  • AEP is necessary and sufficient for optimal processing and presentation of the tetanus toxin C fragment (TTCF) Ag in vitro, but its importance has not been tested in vivo. (jimmunol.org)
  • Moreover, clear relationships between Ags and processing proteases identified from short-term in vitro processing and presentation studies do not necessarily predict an absolute in vivo dependency on those processing enzymes, not least because they may be expressed at strikingly different levels in vitro versus in vivo. (jimmunol.org)
  • Functional assays for the induction of in vitro antigen-specific proliferation of immune catfish peripheral blood leukocytes (PBL) showed that membrane preparations from antigen-pulsed autologous APC were highly stimulatory. (hindawi.com)
  • These recombinant subunit antigens require potent adjuvants or immune modulators to enhance their immunogenicity as well as their capacity to trigger CTLs responses required to fend off life-threatening infections caused by intracellular pathogens, such as HIV, malaria, and tuberculosis [ 6 ]. (hindawi.com)
  • Radiotherapy (RT), an established curative and palliative cancer treatment, exerts potent immune modulatory effects, inducing tumor-associated antigen (TAA) cross-priming with antitumor CD8+ T cell elicitation and abscopal effects. (jci.org)
  • Fig. 6: MARIA scores predict melanoma HLA-II-presented antigens and are associated with post-vaccine CD4 + T cell responses. (nature.com)
  • In turn, this enables the synchronous activation of both CD4 + and CD8 + T cell responses against the cognate antigen, thereby bridging the gap between the humoral and cellular branches of the adaptive immune response. (frontiersin.org)
  • The magnitude of responses elicited with such membrane preparations was very similar to that of PBL cultures stimulated with native antigen-pulsed and fixed intact APC or prefixed intact APC incubated with a peptide fragment of the nominal antigen. (hindawi.com)
  • Altogether, lipid antigen properties make them attractive for their use in subunit vaccines against Mtb. (ipbs.fr)
  • Specificity for antigen detection, uptake, and/or processing is conferred by cellular receptors that may bind to a unique ligand, such as insulin-like growth factor receptor 1 (IGFR1), or to a conserved motif present on many ligands, such as the mannose receptor (MR) DC-SIGN. (frontiersin.org)
  • Use of radiolabeled antigen and subcellular fractionation protocols also showed that antigen localized in endosomes/lysosomes. (hindawi.com)
  • In the present work we investigated the use of mesoporous silicon microparticles (MSMPs) for adjuvant and antigen deliver purposes. (hindawi.com)
  • We previously described that some mycobacterial glycolipid antigens must be processed, however the underlying molecular mechanisms remain poorly defined. (ipbs.fr)
  • This process, essential for the efficacy of therapeutic vaccines, is called cross presentation, and DCs are the main antigen cross presenting and cross priming cell type in vivo [ 11 ]. (hindawi.com)
  • In addition, the efficacy of agents that interfere with antigen presentation process can also be evaluated by SIAT® antigen presentation assay. (creative-biolabs.com)
  • Ethanol inhibits exogenous and allogeneic antigen presentation and affects the formation of peptide-MHCII complexes, as well as altering costimulatory molecule expression on the cell surface. (asm.org)
  • Genes in the MHC that may affect antigen processing. (springer.com)
  • Transcription of genes involved in class I presentation is increased in KS and after infection of LECs, but MHC-I and ICAM-1 surface expression are down-regulated in KLECs. (bloodjournal.org)
  • In contrast, an aspartyl protease inhibitor suppressed the presentation of OVA, an effect attributed to the blockade of cathepsin E ( 10 ). (jimmunol.org)
  • Using this assay, the investigators will analyze the ability to block DQ8 antigen presentation as the dose of Methyldopa changes through the course of the study. (clinicaltrials.gov)
  • Below is a brief description of our workflow of SIAT® antigen presentation assay service. (creative-biolabs.com)
  • Coordinate defects in human histocompatibility leukocyte antigen class II expression and antigen presentation in bare lymphocyte syndrome. (springer.com)
  • This finding implied that depressed effector T-cell functions in the setting of chronic ethanol feeding may be due in part to intrinsic defects in antigen presentation capacity by DCs. (asm.org)
  • Interleukin-2 (IL-2) was measured as an indicator of antigen-specific T-cell activation by DCs in coculture. (asm.org)
  • In each case, ligand binding by the receptor can not only initiate ligand internalization but also trigger additional signaling cascades, which exert direct or indirect effects on subsequent antigen presentation. (frontiersin.org)