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

Responses to the superantigen Mls are characterized by proliferation of a significant percentage of T cells expressing receptors encoded by one or a few V beta gene segments. Apparently similar responses are elicited by the staphylococcal enterotoxins (SEs) and other bacterial superantigens. We have observed that T cells can be stimulated by the bacterial superantigen SEs presented by either spleen cells or fibroblasts transfected with the appropriate MHC class II genes. However, the results in this study showed that T cells required more than 100-fold higher concentrations of SEA in the presence of L cell transfectants than spleen APC, although T cell responses to SEB and several other toxins presented by the two types of APC were equivalent. Thus, L cell transfectants have a selective defect in presenting SEA. These data suggest that fibroblasts lack a component required by SEA to stimulate certain T cells, and lead us to propose an alternative model for bacterial superantigen mitogenesis in which the superantigen binds to and modifies the behavior of an endogenous co-ligand.
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PMID:Stimulator cell type influences the response of T cells to staphylococcal enterotoxins. 790 98

According to some models of T cell education, tolerance, and autoimmunity, recognition of MHC molecules by T cells may depend on the nature of the APC expressing the MHC/Ag complex. To examine this, a panel of 23 I-Ad-restricted, alloreactive T cells were used to probe MHC class II molecules expressed on established lines representing different lineages. Surprisingly, we observed cell type-specific reactivity in the majority of the T cells. In all, 18 different reactivity patterns were identified. The patterns observed suggests that MHC reactivity can be organized into a hierarchical pattern for both the APC and the T cells. Experiments assessing T cells' avidities for allogeneic targets, ability to produce lymphokines, and expression of accessory molecules revealed no predictive correlation with the hierarchical reactivity pattern, nor did experiments measuring allogeneic target cells' expression of known accessory molecules and ability to stimulate Ag-specific hybridomas. These results suggest that the differential reactivity cannot be accounted for by accessory molecule discrepancies among the APC, but rather might reflect deficiencies in the ability of the various APC to engage the Ag-specific T cell receptor. Collectively, these data indicate that a significant fraction of allorecognition of MHC class II is cell-type dependent and that cell-type-specific recognition may relate to peptide-specific recognition requirements by the Ag receptor of alloreactive T cells.
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PMID:T cell receptor recognition of MHC class II alloantigens is highly cell type dependent. 790 4

Although the importance of CD4+ T cells for the induction of an effective CD8+ cytolytic T cell response is well documented, the mechanism by which MHC class II-negative tumor cells recruit CD4+ T help is not well understood. We have previously shown that IL-2 or IFN-gamma gene-modified CMS-5 tumor cells do not grow in syngeneic mice; however, mice which rejected the cytokine-secreting tumor cells develop a protective immune response against a challenge with parental tumor cells. Here we show that rejection of IL-2-secreting CMS-5 cells is not mediated by T cells. However, establishment of a protective immune response against CMS-5 tumor cells requires the presence of both CD4+ and CD8+ T cell subsets during the period of immunization with IL-2-secreting CMS-5 cells as well as during the effector phase. Extensive histologic analysis has failed to detect the presence of T cells at the site of immunization with either IL-2- or IFN-gamma-secreting CMS-5 cells. The main infiltrate at the site of inoculation with IL-2-secreting CMS-5 cells consisted of NK cells that appeared to play a role in their rejection. The predominant infiltrate at the site of inoculation with IFN-gamma-secreting CMS-5 cells consisted of macrophages. These observations argue against a direct role for the intact tumor cell in presenting either T helper or CTL epitopes to the immune system, and support the view that specialized APC are responsible for the in vivo priming of a T cell response against MHC class I-restricted Ag.
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PMID:The role of IL-2 secreted from genetically modified tumor cells in the establishment of antitumor immunity. 790 36

To examine the specificity of T helper cells activated during murine graft-vs-host disease (GVHD), T cell hybridomas from GVHD spleens and livers were generated and analyzed. CTL-depleted C57BL/6 (B6) donor cells were injected into irradiated (B6 x bm12)F1 or (bm1 x bm12)F1 recipient mice. Five or fourteen days later, cells from livers and spleens were fused directly with the TCR-deficient (alpha beta)- BW5147 thymoma line. The in vivo-activated T cells produced hybridomas as efficiently as either T cells activated in a primary mixed lymphocyte reaction or expanded in vitro after isolation from GVHD mice. Overall, 91% (396 of 437) of hybridomas generated from GVHD animals responded to immobilized anti-CD3 and 56% (220 of 396) of these hybridomas responded specifically to APC expressing host bm1 or bm12 alloantigens. More than 80% of bm12-specific hybridomas expressed CD4; all (53 of 53) of the bm12-specific hybridomas tested reacted to homozygous bm12 APC. Of the alloreactive T hybridomas generated from B6-->(bm1 x bm12)F1 GVHD mice, 7% responded to bm1 APC. Five bm1-specific hybridomas were analyzed further. One CD4+ hybridoma recognized a bm1 peptide presented by self I-Ab and was blocked by anti-Ia Ab; the other four hybridomas, two of which also expressed CD4, responded to transfected L cells expressing H-2Kbm1 and were not inhibited by anti-Ia Ab. These results indicate that a high percentage of CD4+ T hybridomas generated from freshly isolated T cells activated in vivo during GVHD are specific for host MHC class II or class I alloantigens.
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PMID:Reactivity of hybridomas derived from T cells activated in vivo during graft-versus-host disease. 796 59

The behavior of mouse I-Ak molecules was studied in the human Ag presentation mutants T2 and 9.5.3, which contain deleted or mutated HLA DM genes. HLA class II molecules expressed by these APC are defective in presentation of native Ag and are mostly complexed with class II-associated invariant chain peptides (CLIP). In contrast to human class II molecules, a significant proportion of mouse I-Ak molecules expressed in T2 and 9.5.3 were associated with antigenic peptides, indicating that I-Ak/peptide assembly is possible in the absence of the Dm proteins. Thus, the presentation of determinants derived from hen egg lysozyme (HEL), keyhole limpet hemocyanin, and conalbumin was normal in 9.5.3Ak and a conalbumin determinant was presented normally by T2.Ak. However, the keyhole limpet hemocyanin determinant was not presented by T2.Ak, and HEL46-61 was only presented at a low level by these APC. SDS-stable, dimeric I-Ak molecules were expressed by both T2.Ak and 9.5.3Ak and formed late in their intracellular transport. Presentation of HEL46-61 was partially inhibited by disrupting vacuolar acidification in 9.5.3Ak, consistent with I-Ak/peptide assembly in a post-Golgi endosomal compartment. Accordingly, Dm is not an obligatory requirement for MHC class II/peptide assembly. We propose that Dm influences the displacement of CLIP from recently synthesized class II molecules, a process that is likely to be less critical for I-Ak because of its low affinity for CLIP.
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PMID:Antigen presentation and assembly by mouse I-Ak class II molecules in human APC containing deleted or mutated HLA DM genes. 798 44

It is known that immunoglobulins can be processed and that idiotypic peptides are presented on MHC class II molecules to T cells. It has also been demonstrated that T cells can recognize a complex of an Id-peptide/MHC molecule as a tumor-specific antigen on B lymphoma cells. However, plasmacytomas, an important type of B cell malignancies, most often lack class II molecules and are thus expected to be poor targets for Id-specific, CD4+ T cells. Nevertheless, we now demonstrate that cloned, MHC class II restricted T cells, specific for a lambda 2(315) idiotypic peptide, convey protection in vivo (Winn assay) against the class II molecule-negative MOPC315 (alpha, lambda 2(315)) plasmacytoma. T cells can also inhibit the growth of MOPC315 cells in vitro provided that MHC compatible (H-2d) splenocytes and extra lambda 2(315) are added. Based on these data we suggest that the myeloma protein secreted by MOPC315 cells attains such a high local concentration in vivo that it is processed and presented by neighboring host APC to the Id-specific T cells. Such activated T cells secrete lymphokines which may directly affect the growth of MOPC315 cells in the vicinity. Alternatively, lymphokines from activated T cells stimulate local host cells, like macrophages, to become tumoricidal.
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PMID:The role of idiotype-specific, CD4+ T cells in tumor resistance against major histocompatibility complex class II molecule negative plasmacytoma cells. 809 65

IL-10 is a product of activated keratinocytes and is released during the induction phase of contact sensitivity. As IL-10 effects have been described as being mediated by APC, we investigated effects of IL-10 on epidermal Langerhans cells (LC), the resident APC in the epidermis. Initial studies failed to demonstrate effects of IL-10 on MHC class II Ag expression by LC or anti-CD3 mAb- or alloantigen-induced LC-dependent T cell proliferation. However, production of IFN-gamma and IL-2, (but not IL-6) was markedly reduced in these assays. When the soluble-protein Ag specific T cell clones AE7 (Th1) and D10.G4 (Th2) were substituted for unprimed T cells, differential effects of IL-10 on T-cell proliferation were observed. Whereas IL-10-pretreated and untreated LC supported Th2 cell proliferation equally well, IL-10-pretreated LC were essentially unable to induce Th1 cell proliferation in response to native protein or peptide Ag. The inhibitory influence of IL-10 on Th1 cells was observed when fresh or 1 day cultured LC were used; 2- or 3-day cultured LC were affected to a much lesser extent by IL-10 pretreatment. Further, coculture experiments using IL-10-pretreated or untreated LC of a different haplotype suggest that IL-10 negatively regulates a costimulatory signal required for induction of Th1 cell proliferation. To assess whether T cells incubated with Ag and IL-10-pretreated LC were responsive to further stimulation, T cells were rescued after 1 day of coculture with IL-10-pretreated LC and restimulated, either immediately or after 1 to 5 days of rest, with untreated LC in the presence of Ag. T cells incubated with IL-10-pretreated LC were found to be anergic, whereas T cells incubated with untreated LC proliferated normally after further stimulation. However, anergic T cells responded vigorously to IL-2. These data indicate that although IL-10-pretreated LC are effective APC for Th2 cells, they fail to induce Th1 cell proliferation and rather induce clonal anergy in these cells.
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PMID:Inhibition of Langerhans cell antigen-presenting function by IL-10. A role for IL-10 in induction of tolerance. 810 65

Processing of proteins into immunogenic forms and their subsequent presentation to T cells are mediated by APC. Monocytes and macrophages have long been recognized as one of the APC types. However, little is known about whether functional heterogeneity in processing and presentation exist within the monocyte/macrophage population. Past difficulties in obtaining clonal representatives of these populations have limited investigations in this regard. The c-myc-containing retrovirus MRV, previously shown to immortalize murine macrophages, was used to generate a large panel of macrophage cell clones. Differences observed in cell surface antigen expression and morphology demonstrated phenotypic heterogeneity among these clones. Functional heterogeneity was also observed both before and after IFN-gamma and IL-4 stimulation. The clones differ in their capacity to present several nominal antigens to T cell hybridomas. When parallel variation in ability to present both a nominal antigen and a peptide representing the epitope for which a T cell hybridoma was specific was observed among the clones, this variation correlated with the levels of surface MHC class II antigen the clones expressed. In contrast, diversity in the ability to process and present certain nominal antigens among clones that all presented the corresponding antigenic peptide with similar efficiency did not appear to be due to differences in levels of surface MHC class II molecules. Our results suggest that the macrophage clones are heterogeneous in their ability to both process and present several antigens. The ability to obtain macrophage tissue culture cell lines displaying phenotypic and functional heterogeneity should allow insight into the impact of normal macrophage heterogeneity on the outcome of immune responses in vivo.
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PMID:Monoclonal c-myc transformed macrophage cell lines. I. Heterogeneity in ability to process and present antigen. 810 18

Cells of the macrophage lineage are required to cope with bacterial infection and to serve as APC for T lymphocytes. Among the regulatory factors limiting the macrophage response to infection and the expansion of Ag-specific T cells, IL-10 has received recent attention. On monocytes/macrophages, IL-10 has been shown to inhibit the intracellular killing of bacteria, the secretion of cytokines, and the expression of MHC molecules. In the present study we have examined the effect of IL-10 on different APC obtained from the central nervous system. Both, astrocytes and microglial cells are in a resting state and require activation signals to express MHC class II and cytokine genes. Whereas IL-10 profoundly inhibits the IFN-gamma-induced expression of MHC class II Ag on microglial cells, it had no such effects on astrocytes. Nevertheless, IL-10 suppressed the MHC class II- and Ag-dependent proliferative response of T cells in the presence of both types of APC. As shown by the use of anti-IL-10 Abs, endogenously produced IL-10 influenced the function of microglia but not of astrocytes to serve as APC. IL-10 significantly inhibited the LPS-induced production of granulocyte-macrophage-CSF, macrophage-CSF, and IL-6 by both astrocytes and microglial cells. In contrast, the secretion of these cytokines by the two glial cell population was not altered by IL-10 when IL-1 beta, TNF-alpha, or viruses were used as stimuli.
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PMID:Antigen presentation in the central nervous system. The inhibitory effect of IL-10 on MHC class II expression and production of cytokines depends on the inducing signals and the type of cell analyzed. 814 79

A working model for the action of superantigens (SAg) is that they are simple proteins having binding sites for both MHC class II molecules and the V beta domain of the TCR. Binding of a SAg to both molecules cross-links the TCR, inducing a biologic response. In this study, we have tested this working model using a SAg mimic consisting of a hybrid Ab bispecific for the murine MHC class II molecule I-E and the V beta 8 domain of the murine TCR. The bispecific Ab activates V beta 8-bearing T cells only in the presence of I-E molecules on APC when tested in vitro. The effect of the bispecific Ab in vivo revealed both clonal deletion and a reduction in the responsiveness of V beta 8-bearing T cells. Thus, the results suggest that molecules distinct from SAg that can bind to both MHC class II molecules and the V beta domain of the TCR can mimic the biologic actions of a SAg.
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PMID:Superantigen-like properties of an antibody bispecific for MHC class II molecules and the V beta domain of the T cell antigen receptor. 814 52


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