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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The bacterial toxic mitogens or superantigens are a family of related proteins that elicit potent T cell proliferative responses. These responses require APC that express MHC class II proteins, but they are not MHC restricted and they do not depend on a processing step, presumably because these mitogens bind directly to MHC class II molecules. These mitogens stimulate T cells by interacting in an unknown way with the portion of the TCR encoded by certain V beta gene segments. In this paper, we explore the importance of MHC class II polymorphism in T cell responses to staphylococcal enterotoxins. We find that certain MHC molecules present SEB to V beta 8-bearing T cells far better than others. These data suggest that one route of host defence against bacterial toxic mitogens may be to alter MHC class II molecules so that stimulation is inhibited.
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PMID:Control of T cell responses to staphylococcal enterotoxins by stimulator cell MHC class II polymorphism. 190 96

Acetylcholine receptor-(AcChR) specific T cell lines were propagated from the PBL of six myasthenia gravis (MG) patients by the use of a pool of synthetic peptides (alpha-pool) corresponding to the complete sequence of the alpha-subunit of the human AcChR. All the lines had CD4+ phenotype and strongly recognized the alpha-pool. Four lines cross-reacted with native Torpedo AcChR. Five lines showed, at certain stages of their propagation, some degree of reactivity to autologous or DR-matched APC. One of the CD4+ T lines was challenged with each one of the peptides present in the alpha-pool. Several peptides, corresponding to the sequence segments 48-67, 101-120, 304-322, 320-337, and 419-437 of the human alpha-subunit were recognized, indicating that different epitopes and multiple T cell clones are involved in the recognition of the autoantigen in MG. Human AcChR-specific CD4+ T cell lines will be useful to identify the repertoire of epitopes recognized by the autoreactive Th cells in MG, to investigate the TCR genes utilized by autoreactive Th cells and to develop specific immunosuppressive treatments using anti-T cell vaccination.
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PMID:Use of synthetic peptides to establish anti-human acetylcholine receptor CD4+ cell lines from myasthenia gravis patients. 196 87

The role of leukocyte function-associated Ag-1 (LFA-1) in intercellular adhesion is well documented. Previously, we demonstrated that the LFA-1 molecule (CD11a/CD18) can also regulate the induction of proliferation of peripheral blood T cells. In these studies, we observed opposite effects of antibodies against CD11a (LFA-1-alpha-chain) or CD18 (LFA-1-beta-chain). Here, we determined the effects of anti-CD11a and anti-CD18 mAb on proliferation of cloned influenza virus-specific T cells. Anti-CD18 mAb had similar inhibiting effects on the proliferative response of T cell clones induced by immobilized anti-CD3 mAb as it had on the response of peripheral blood T cells. In contrast to its costimulatory effect on resting peripheral blood T cells, anti-CD11a mAb did not increase the proliferation of cloned T cells. Similar differences in effects of anti-CD11a and anti-CD18 mAb were observed when proliferation of the T cell clones was induced by immobilized anti-TCR mAb. When proliferation was induced by influenza virus presented by monocytes as APC, both anti-CD11a and anti-CD18 mAb inhibited T cell proliferation. However, when EBV-transformed B cells were used as APC, neither anti-CD11a nor anti-CD18 mAb inhibited proliferation. These results demonstrate that the effects of antibodies against CD11a (LFA-1-alpha) or CD18 (LFA-1-beta) on T cell proliferation depend on 1) the stage of activation of the T cells, 2) the activation stimulus and its requirement for intercellular adhesion involving LFA-1, and 3) the type of cell used to present Ag.
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PMID:Analysis of the role of leukocyte function-associated antigen-1 in activation of human influenza virus-specific T cell clones. 197 Mar 49

To further the understanding of the role of T cells in immunity to the parasite Toxoplasma gondii, antigen-specific T cell clones were generated using peripheral blood mononuclear cells from seropositive individuals. Whole parasites were used to stimulate a proliferative expansion of antigen-reactive cells, followed by limiting dilution cloning in the presence of irradiated, autologous PBMC and rIL-2. Three parasite antigen-specific T cell clones expressing the CD3+ phenotype were selected for further characterization. Phenotypic analysis with monoclonal antibodies revealed two clones reactive with CD8 (RTg1 and RTg3) while the other (RTg2) phenotyped as CD4+, CD8-. When tested in a proliferation assay using a panel of different T. gondii proteins, clone RTg1 reacted with a single large protein (Mr greater than 180,000) as well as smaller components (less than 12,000), clone RTg2 reacted with a protein of Mr = 28,000 and clone RTg3 reacted with a protein of 116,000 plus smaller components (less than 12,000). Only the 28,000 = Mr antigen recognized by RTg2 was reactive on Western blot with autologous donor antisera. All three clones produced IFN-gamma and IL-2 in varying amounts upon antigenic stimulation in the presence of irradiated APC. Moreover, one clone RTg1, exhibited direct parasite cytotoxicity, inhibiting extracellular T. gondii by greater than 70% when incubated at an effector/target ratio of 40:1. This clone was alpha, beta TCR heterodimer positive and exerted its cytotoxic parasiticidal activity in the apparent absence of MHC restriction. The results provide evidence for the existence of circulating antigen-specific cytotoxic T cells in normal humans who are toxoplasma antibody seropositive.
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PMID:Induction of antigen-specific human cytotoxic T cells by Toxoplasma gondii. 197 29

A CD8+ Ts clone 13G2 was established from lymph node cells of bovine alpha s1-casein-primed C57BL/6 mice by in vitro antigenic stimulation followed by maintenance with IL-2-containing medium. The clone suppressed the Ag-induced proliferative responses of CD4+ Th cell clones without detectable cytotoxicity for both APC and responding T cells. The clone was able to suppress the in vitro proliferative response and antibody formation of Ag-primed lymph node cells. The suppression was Ag-nonspecific and not restricted to the MHC. The clone was able to suppress the proliferation of Th clones induced by an immobilized anti-TCR antibody in which APC was absent. The clone was, however, unable to suppress the proliferation of Th clones induced by anti-CD3 or IL-2. Thus, the mechanism of suppression by 13G2 was found to be due to a direct action on Th by inhibiting a consequence of signal transduction initiated through the TCR.
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PMID:CD8+ suppressor T cell clone capable of inhibiting the antigen- and anti-T cell receptor-induced proliferation of Th clones without cytolytic activity. 197 94

The seminal observation made 30 years ago that T cells do not discriminate between native and denatured proteins, whereas B cells generally do, can now be explained by the fact that T cells never see antigens in their native conformation and that intact proteins cannot associate simultaneously with MHC molecules and the TCR. This difference in the ability to recognize antigen based on conformational specificity appears to be a consequence of the fact that the T cell sees antigen not free in solution, but on the surface of an APC in association with MHC molecules. The metabolic events that protein antigens undergo within APC, prior to their presentation in an appropriately processed form to T cells, are called antigen processing. The end-product of antigen processing for CD4+ T cells is a relatively short peptide fragment bound to class II MHC molecules on the surface of an APC that can be recognized by the TCR on the T cells. Because this event is difficult to monitor directly, antigen processing can only be assayed in conjunction with the temporally distal event of T-cell activation, manifested ultimately as proliferative responses or lymphokine secretion. In addition to occupancy of the TCR by the peptide/class II complex, several other antigen-nonspecific receptor-ligand interactions between APC and T cells are required for optimal T-cell activation. M phi, B cells, and LC/DC comprise the principal APC for CD4+ T cells. M phi and B cells have been studied extensively with respect to their antigen processing and presenting capacities. Only recently, however, have such capacities been investigated in LC and DC; these studies now indicate freshly isolated LC (but not cultured LC and DC) to possess efficient antigen processing capabilities. In this respect, LC have been proposed to represent evolving (or "maturing") forms of DC: Freshly isolated LC (which retain morphologic and functional properties of epidermal LC in situ) are the equivalent of tissue forms of DC, whereas cultured LC resemble lymphoid or circulating DC. Cultured LC and DC appear to be the sole effective APC for inducing primary T-cell responses in vitro. Possibly underlying this property is the ability of cultured LC and DC (but not M phi, B cells, or freshly isolated LC) to induce formation of T-cell clusters during the course of such responses. The capacity of accessory cells to function as APC varies depending upon the type of APC and T cells examined.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antigen processing and presentation by epidermal Langerhans cells. Induction of immunity or unresponsiveness. 197 19

The contributions of the amino acids at 13 polymorphic positions in the HLA-DR7 beta 1 chain to T cell recognition of two antigenic peptides of tetanus toxin (p2 and p30) were assessed using transfectants expressing mutant DR7 beta 1 chains as APC for six toxin-specific T cell clones with two different restriction patterns: monogamous (restricted by DR7 only) or promiscuous (restricted by DR7; DR1; DR2, Dw21; and DR4, Dw4). Each of the 13 substitutions significantly decreased or eliminated the ability of the DR7 molecule to present a peptide to one or more of the T cell clones, but none of the substitutions abolished recognition by all clones. Interestingly, substitutions at positions 4 and 25, which are predicted in the class II model to be located outside the peptide binding groove, decreased the ability of the DR7 molecule to present Ag to some clones but not to others. Each of the four clones specific for the p2 peptide and the two clones specific for peptide p30 had a different reactivity pattern to the panel of DR7 beta 1 mutants, indicating that the TCR of each clone has a different view of the p2/DR7 or p30/DR7 complex. These data emphasize the complexity of the interactions of multiple residues in DR7 beta 1 chains in Ag-specific T cell recognition.
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PMID:Antigen-specific T cells with monogamous or promiscuous restriction patterns are sensitive to different HLA-DR beta chain substitutions. 204 Jul 99

Most foreign antigens are "processed" by APC into a form in which they can bind MHC molecules and be recognised by the TCR. Functional and immuno-gold labelling studies have been used to determine the putative sites of MHC-Ag interaction following uptake of Leishmania donovani into a phagolysosome. During infection with this parasite in vivo, upregulation of class II occurs. Based on studies using scid mice, NK cells appear to contribute little to this process. During chronic infection, however, APC function is diminished in spite of high class II levels. We propose that a lack of coordinate costimulator expression may lead to subsequent loss of T cell function late in infection, by a mechanism involving the induction of T cell unresponsiveness.
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PMID:Antigen processing and presentation: modelling with Leishmania. 204 30

IgA isotype responses are regulated by at least two compartments including those of CD4+ Th2 type cells and cytokines produced by these cells. Interaction of CD4+ Th cells and APC via TCR and Ag-MHC II leads to activation of Th2 type cells. This would allow for secretion of cytokines, especially IL-5 and IL-6 which are key cytokines for the terminal differentiation of B cells into Ig secreting cells. Further, expression of Fc alpha RII on CD4+ Th2 cells could be important for the recruitment of sIgA+ B cells which would allow selective interactions of Th2 cells and sIgA + B cells via Fc alpha RII. This could lead to selectively transfer of IL-5 and IL-6 to sIgA + B cells from CD4+ Th2 cells.
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PMID:Immunoregulatory confluence: T cells, Fc receptors and cytokines for IgA immune responses. 210 7

T cell binding to target cells involves not only the TCR and its MHC-bound ligand, but also a collection of additional proteins on both the T cell and its target. In an attempt to identify new molecules involved in this binding, mAb were raised against APC, and screened for their abilities to inhibit T cell recognition of Ag plus MHC on B cells. Six antibodies were identified that inhibited this reaction and that bound a cell-surface glycoprotein (Lgp55), with core polypeptide Mr 30,000 and a glycosylated Mr of approximately 55,000 depending upon the cell source. The properties of Lgp55 were consistent with it being the mouse homologue of a recently identified human ligand (intercellular adhesion molecule-2) for lymphocyte functional Ag-1 because the proteins are of comparable Mr, and antibody to Lgp55, like anti-lymphocyte functional antigen-1, blocks T cell recognition of Ag presented by B cells, but not of Ag presented by mouse fibroblasts.
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PMID:Identification of a new cell surface glycoprotein with accessory function in murine T cell responses. 213 99


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