Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent attention has focused on the role keratinocytes (KC) may play in the induction of T cell-mediated inflammatory responses in skin, particularly because KC, when activated by immunologic stimuli, express MHC class II Ag and secrete immunomodulatory cytokines. We tested the capacity of normal human KC that were stimulated with PMA to induce PBMC proliferation. PMA-treated, but not untreated, KC induced proliferation of allogeneic as well as autologous PBMC; in addition, when purified CD4+ or CD8+ T cells were used as responders, each subset proliferated. PBMC proliferation was not due to direct action of PMA on PBMC, nor to contamination of KC cultures with Langerhans cells (LC) or dermal APC. Pretreatment with different protein kinase C inhibitors abrogated the capacity of PMA-stimulated KC to induce proliferation. Paraformaldehyde-fixed PMA-KC stimulated PBMC proliferation, whereas supernatants from PMA-treated KC failed to do so, indicating that a membrane-associated activity on PMA-KC contributes to the induction of PBMC proliferation. PMA induced intercellular adhesion molecule-1 (ICAM-1) expression on KC; furthermore, mAb against ICAM-1 or against its ligand lymphocyte function-associated Ag (LFA-1) (CD11a/CD18) significantly, but incompletely, reduced the stimulatory capacity of PMA-treated KC, indicating that ICAM-1/LFA-1 interaction contributed to PBMC proliferation. IFN-gamma or TNF-alpha also induced ICAM-1 on KC, but these KC failed to stimulate proliferation, suggesting that PMA induces additional signals from KC, which act in concert with ICAM-1 to promote proliferation. Finally, mAb against HLA-ABC or HLA-DR did not inhibit proliferation. We conclude that PMA can activate KC to stimulate T cell proliferation in a MHC-independent fashion. This activation is mediated by protein kinase C and in part by the induction of ICAM-1 expression on KC.
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PMID:Phorbol myristate acetate-activated keratinocytes stimulate proliferation of resting peripheral blood mononuclear lymphocytes via a MHC-independent, but protein kinase C- and intercellular adhesion molecule-1-dependent, mechanism. 167 Sep 43

We have directly compared the signals required for: induction of the [Ca+2]i response, expression of Tac antigen, and proliferation in antigen-specific human T cell clones. We have previously shown that antigen-specific activation of cloned T cells under conditions leading to proliferation is accompanied by a rapid increase in [Ca+2]i. Cloned T cells showed increased [Ca+2]i, enhanced Tac expression, and proliferated in response to specific antigen in the presence of viable, genetically appropriate antigen-presenting cells. Paraformaldehyde fixation of antigen-presenting cells after "pulsing" with antigen prevented proliferation, but did not affect MHC-restricted [Ca+2]i or Tac responses. Treatment of cloned T cells with monoclonal anti-T3 antibody also increased [Ca+2]i and Tac expression but did not induce proliferation. Proliferation was restored by viable autologous or allogenic APC or exogenous IL 2, but not by IL 1. In contrast to resting T cells, T cell clones were insensitive to the mitogenic effects of lectins or of ionophores and phorbol esters. These results suggest that activation of antigen-specific T cells requires the sequential action of at least two signals. The first is MHC restricted and is mediated by interaction of antigen + MHC class II products with the T cell receptor (T3-Ti) complex. This leads to Tac expression and increased [Ca+2]i, but is not sufficient for proliferation. This signal can be bypassed by anti-T3 monoclonal antibodies. Proliferation requires a second, nonantigen-specific, non-MHC-restricted antigen-presenting cell signal, which cannot be replaced by IL 1 in our system. This signal can be bypassed, however, by the addition of exogenous IL 2 to cells that have received the first signal and express Tac, suggesting that it is required for IL 2 synthesis and secretion. T cell clones therefore provide a useful model for studying antigen-dependent and -independent events in cell activation.
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PMID:Antigen-specific and -nonspecific mitogenic signals in the activation of human T cell clones. 295 89

The hapten- and carrier-specific T lymphocyte clone D5 and a T hybridoma (D5h) derived from D5 cells recognize several different protein Ag conjugated with p-azobenzenearsonate (arsonate) presented by the class II MHC protein I-Ad. We show here that the ligand recognized by the D5 TCR is a complex of a haptenated peptide bound to I-Ad. We have identified a peptide fragment generated by enzymatic cleavage of arsonate-conjugated OVA (Ars-OVA), which stimulates D5 cells when presented by I-Ad-bearing APC. A synthetic peptide corresponding to this fragment, OVA(36-50), forms a ligand for D5h cells when it is conjugated with arsonate and presented by cells bearing I-Ad. Paraformaldehyde-fixed, I-Ad-bearing cells present Ars-OVA(36-50), or the longer stimulatory peptide Ars-OVA(33-49), to D5h cells, demonstrating that haptenated synthetic peptides can substitute for naturally processed antigenic peptides. The peptide Ars-OVA(33-49) binds to the major peptide-binding site of I-Ad because it competitively inhibited presentation of the peptide OVA(323-339), previously demonstrated to bind to I-Ad directly in vitro, to the OVA/I-Ad-specific T cell hybridoma 3DO-54.8. The unconjugated OVA(33-49) peptide failed to inhibit the presentation of OVA(323-339), demonstrating that the hapten facilities binding of the peptide to I-Ad. Conversely, the peptide OVA(323-339) competitively inhibited the presentation of Ars-OVA(33-49) to D5h cells, indicating that the two peptides Ars-OVA(33-49) and OVA(323-339) bind to overlapping sites on I-Ad. Amino acid substitutions introduced into the beta 1 domain of I-Ad that affected recognition of OVA(323-339) by 3DO-54.8 cells also affected recognition of Ars-OVA(33-50) by D5h cells, demonstrating that similar regions on I-Ad are required for TCR recognition of conventional as well as haptenated peptides. These results represent the first demonstration that the ligand recognized by a hapten- and carrier-specific T cell clone restricted to an MHC class II protein is a haptenated peptide Ag bound to the MHC molecule.
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PMID:Nature of the ligand recognized by a hapten- and carrier-specific, MHC-restricted T cell receptor. 768 84

The role of endosomes in exogenous Ag processing was investigated by targeting Ag into the endosomal transport pathway via transferrin receptors. The Ag, pigeon cytochrome c and chicken OVA, were coupled to human ferric transferrin by a heteroligation technique. The conjugates were significantly more efficient than native Ag in stimulating Ag-specific CD4+ T cells, when the APC expressed transferrin receptors. The addition of ferric transferrin eliminated the enhanced response. Paraformaldehyde-fixed APC did not present the conjugates, indicating that the conjugates still required processing to activate T cells. An augmented level of T cell activation was not observed when the APC lacked transferrin receptors or when the conjugate contained the apoenzyme form of transferrin, which does not bind the receptor. The conjugate followed an intracellular pathway similar to that for transferrin, remaining in low density vesicles. Degraded conjugate appeared rapidly in culture supernatants, within 5 min, and peaked by 20 min; under these conditions a T cell response to the conjugate was elicited that was consistent with an early processing compartment. Our results suggest that antigenic peptide fragments can be generated in the early endosomes, without delivery of these Ag to the lysosomes. Thus, various Ag may have differential processing requirements, dictated by their molecular nature, that determine the site of Ag processing.
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PMID:Exogenous antigens internalized through transferrin receptors activate CD4+ T cells. 809 28

We isolated CD4+ and CD8+ T cell clones from pancreatic islets of non-obese diabetic (NOD) mice and studied their interactions with pancreatic islets, in culture. The three CD4+ T cell clones proliferated when cultured with islet cells from NOD, BALB/c, or C57BL/6 (B6) mice. For proliferation to the allogeneic islets, however, APC from NOD mice were required in the culture. Two of the clones also produced IFN-gamma upon culture with NOD islet cells. The Ag from islet cells responsible for T cell stimulation were not released into the supernatant but were cell associated. Paraformaldehyde treatment of islet cells, in fact, preserved their antigenicity. The fixed islet cells could present Ag to CD4+ T cell clones, provided live, syngeneic APC were added to the culture. We conclude from these experiments that islet cells donate Ag to the APC for presentation and that the function of APC is to process the Ag. The two CD8+ T cell clones proliferated and released IFN-gamma upon reaction with islet cells from either NOD or BALB/c but not B6 mice. The CD8+ T cell clones also reacted with the insulinoma NIT-1 cell line, derived from NOD mice. Fixation of NIT-1 cells did not impair recognition when live APC were present in the culture. In this case, however, the APC could be allogeneic. We conclude that CD8+ T cells directly recognized a MHC class I-restricted Ag on target cells, but needed the costimulatory effect of APC. We also found that CD8+ T cells killed islet cells. Two of the CD4+ T cell clones produced diabetes when transferred into male, irradiated NOD mice. For optimal transfer of disease, the CD4+ T cell clones had to be co-injected with CD8+ T cells from NOD diabetic mice. The two CD8+ T cell clones did not transfer disease.
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PMID:Presentation of beta-cell antigens to CD4+ and CD8+ T cells of non-obese diabetic mice. 810 46