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

Immunization of naive or specifically primed C3H/HEJ with irradiated B10.BR spleen cells via the hepatic portal vein leads to an antigen specific decrease in the proliferative and cytotoxic response to B10.BR antigen assayed in vitro (and to increased graft survival of B10.BR grafts in vivo). This effect seems to be mediated in the main by a decrease in IL-2 production from CD4+ T lymphocytes of mice given antigen by the portal route, which is in turn caused by a decreased precursor frequency of IL-2-producing cells. No clear decrease in IL-4 production was seen. Hepatic APC isolated from mice receiving antigen via the portal vein were unable to induce IL-2 production from a C3H/HEJ anti-B10.BR cell line in vitro, in contrast to splenic APC derived from the same mice. Even when antigen was given by conventional (systemic) intravenous routes (in this case via the lateral tail vein) hepatic APC isolated from those mice were unable to stimulate IL-2 production from this cell line. Furthermore, 24 h exposure of a cell line to antigen pulsed hepatic APC left those cells refractory to a subsequent restimulation with antigen presented by splenic APC. Spleen lymphoid cells from primed mice challenged in vivo with B10.BR liver cells (i.v.) were similarly unable to produce IL-2 on rechallenge in vitro with irradiated B10.BR spleen cells, though no defect was seen if in vivo challenge was with B10.BR spleen cells. These data imply that presentation of multiple minor cell surface antigens by hepatic APC leads to specific anergization of IL-2 producing T cells, in a fashion which seems to be distinct from that previously reported as due to 'veto-like' activity.
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PMID:Immunosuppression induced by hepatic portal venous immunization spares reactivity in IL-4 producing T lymphocytes. 142 92

We have previously shown that immunization of C57BL/10 (H-2b) mice with the tobacco mosaic virus protein (TMVP) or with its tryptic peptide number 8, representing residues 93-112 of TMVP, induces T cells which proliferate in vitro in response to TMVP and peptide 8. In contrast, immunization of congenic B10.BR (H-2k) mice with either TMVP or with peptide 8 induces T cells which respond in vitro to the homologous but not the heterologous antigen. The capacity to exhibit cross-reactivity between TMVP and peptide 8 on the T cell level has been shown to be under major histocompatibility complex (MHC)-linked genetic control. The lack of cross-reactivity has been attributed to the inability of the H-2k APC to present the appropriate epitope to T cells. In the present paper, we report results of a comparative analysis of the role of structural aspects of the epitope on the proliferative T cell responses from TMVP and peptide 8-immune C57BL/10 (H-2b) and B10.BR (H-2k) mice. Utilizing a panel of synthetic peptides representing portions of peptide 8 and a panel of peptide-protein conjugates, we have determined that peptide 8-immune T cells of the H-2k strain appear to recognize a single epitope within peptide 8, located at its N-terminus. In contrast, in the H-2b strain, both TMVP and peptide 8-immune T cells appear to recognize two overlapping epitopes within peptide 8; one located in the middle region and the other toward the N-terminus. Experiments with H-2b T cells revealed that random amino acids added to the carboxyl or amino-terminus of nonstimulatory peptides can confer activity to these peptides, demonstrating limited specificity of interaction between antigen and Iab. Results of experiments dealing with fixation of antigen-presenting cells suggest that TMVP requires processing in order to be recognized by peptide 8-immune H-2b proliferative T cells whereas peptide 8 does not. Taken together the results suggest that the T cell responsiveness to TMVP and peptide 8 exhibited by these two congenic strains H-2b and H-2k is not only controlled by the strains MHC but is also influenced by antigen processing. Antigen processing may eliminate a potential epitope for the primary induction and the secondary stimulation of B10.BR T cells.
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PMID:Structural aspects of a protein epitope and their role in the major histocompatibility complex control of T cell responsiveness. 170 27

Presence of the three major pathways (self-Ia restricted, allo-K/D restricted, and allo-Ia restricted pathways) in generating class I-restricted CTL has been reported. The present study was conducted in order to clarify which of the three is the main pathway in mediating tumor allograft rejection. One million EL-4 tumor cells derived from C57BL/6 (B6;H-2b) were inoculated into the various strains of mice that were genetically different from B6. Class I (K/D) Ag-disparate but IA Ag-matched B6.C-H-2bm1 (bm1;Kbm1, IAb, IE-, Db) mice or B10.A (5R) (5R; b, b, k, d) mice could not reject 1 x 10(6) EL-4 tumor cells in spite of the strong generation of CTL against the B6 Ag, suggesting the inability of the self-Ia restricted pathway and the allo-K/D restricted pathway in rejecting tumor allografts. The strains of mice being capable of rejecting EL-4 tumor were disparate from B6 mice in both class I and class II (IA) Ag, suggesting the importance of the allo-Ia restricted pathway in rejecting tumor allografts. To generate CTL against Kb Ag via the allo-Ia restricted pathway in the bm1 mice, 2 x 10(7) B6.H-2bm12 (bm12; b, bm12, -, b) spleen cells were injected into the bm1 mice as a supplementary source of allogeneic APC that possibly raise CTL through CD4+ Th cells of bm1 origin. These bm1 mice became capable of rejecting 1 x 10(6) EL-4 tumor cells. The same was observed in the combination of bm12----B10.A (5R) (b, b, k, d) mice. To further elucidate the role of the class II restricted CD4+ Th cells, anti-CD4 antibody was repeatedly i.v. administered into the C3H/He (C3H; H-2k) or the DBA/2 (DBA; H-2d) mice on days 0, 1, and 4. Injection of anti-CD4 antibody led 1 x 10(6) EL-4 tumor cells to grow and kill the C3H and DBA mice. These results suggest that the main effector CTL pathway involved in tumor allograft rejection is allo-Ia restricted pathway where CD8+ precursor CTL were stimulated by the class II-restricted CD4+ Th cells.
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PMID:Tumor allograft rejection is mainly mediated by CD8+ cytotoxic T lymphocytes stimulated with class I alloantigens in cooperation with CD4+ helper T cells recognizing class II alloantigens. 196 30

APC activity of spleen cells from C57BL/10 (B10) mice infected with LP-BM5 murine leukemia virus (MuLV), which is known as a murine acquired immunodeficiency syndrome (MAIDS) virus, was investigated. The ability of splenic APC from LP-BM5 MuLV-inoculated B10 mice to induce soluble Ag-specific proliferation of cloned Th cells was decreased progressively during the infection. The APC defect was found to be due neither to the decreased expression of Ia Ag nor to the insufficient production of IL-1. It was demonstrated that cloned Th stimulated with virus-infected splenic APC displayed the increased [Ca2+]i with severely decreased inositol phospholipid metabolism, which probably led to the defect of Th proliferative responses. These results suggested that the failure of Th to respond to soluble Ag in MAIDS is at least in part due to a selective defect in signal transduction caused by abnormal APC.
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PMID:A selective signaling defect in helper T cells induced by antigen-presenting cells from mice with murine acquired immunodeficiency syndrome. 215 66

The immune responses of B10.A and B10.A(3R) strains of mice to a synthetic variant of moth cytochrome c 86-103 were compared, and an immune response difference between the two strains was found. When T cell hybridomas were made from both strains it was found that the responsive T cells showed degenerate MHC restriction. The hybridomas from B10.A(3R) mice consistently showed a specificity pattern, when tested with allogeneic B10.A APC, different from that seen when syngeneic B10.A(3R) APC were used. The difference in the immune responses of the two strains of mice could be attributed to this APC-expressed specificity. The results were analyzed to determine whether the portion of the antigen that effected T cell memory (the epitope) and the portion that effected APC-expressed specificity (the agretope) were independent. It was found that a) these sites overlap and b) the APC-expressed specificity (i.e., the specificity of agretope recognition) was dependent on the T cell clonotype. This implies that the agretope is not an independent parameter in the process of MHC-restricted antigen recognition. Therefore its employment as an explanation for various phenomena will be limited by the likelihood of circularity.
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PMID:The sites of antigen-T cell and antigen-MHC interactions overlap. 241 83

(CBA X B10)F1 [(H-2k X H-2b)] mice produce two types of antigen-specific T-suppressor factor (TsF), which can be separated by affinity chromatography on anti-I-J monoclonal antibody. After reduction and alkylation, both chains of F1 TsF are required for biological activity. However, the antigen-binding chain (AgBC) of F1 TgFk (AgBCk) is only complemented by I-Jk and likewise for F1 TsFb. In other words, interchain complementation shows the same genetic restriction in interchain complementation in parental and F1 mice. F1 TsF bearing, for example, I-Jk (TsFk), interacts with haptenized 'antigen-presenting cells' ('APC') and parental I-Jk chains interacts with haptenized 'APC' of both parental haplotypes (dual reactivity). In contrast, the combination of parental AgBCb and F1 I-Jb shows single reactivity and only interacts with haptenized 'APCb'. It was inferred that the antigen-binding chain is responsible for the dual reactivity and, hence, for the interaction with a member of the I-J hierarchy on the 'APC'. It was concluded that the antigen-binding chain of TsF has two recognition sites for members of the I-J hierarchy--one for interchain complementation and the other for interaction with the haptenized 'antigen-presenting cell'. The term member of the I-J hierarchy is used instead of I-J because it is not clear whether the AgBC interacts with I-J or a receptor for I-J, or indeed a receptor for that receptor.
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PMID:General considerations in the interpretation of I-J genetic restrictions: evidence that the antigen-binding chain of antigen-specific T-suppressor factor has two recognition sites for members of the I-J hierarchy. 244 88

Previous experiments have demonstrated that the immune response of MHC congenic mice to pigeon cytochrome c is under Ir gene control. Expression of I-E-encoded gene products influences both the magnitude and fine specificity of the Th cell response to pigeon cytochrome c and phylogenetic derivatives. Results of those experiments implicate both determinant selection and repertoire selection as mechanisms of Ir gene control in this system. In this report we have compared the TCR expressed in pigeon cytochrome c-reactive Th cells from B10.A(I-Ek), B10.A(5R) (I-Eb), and B10.S(9R) (I-Es) mice. The B10.A(5R) strain is a low responder to pigeon cytochrome c, but in response to moth cytochrome c this strain produces T cells which respond to pigeon or moth cytochrome c on B10.A APC. These cells are phenotypically identical to the predominant clonal phenotype seen in the B10.A response to pigeon cytochrome c. In this report, we show that the B10.A and B10.A(5R) pigeon cytochrome c-reactive T cells express essentially identical T cell receptors. These results, coupled with recent studies reporting a relatively low affinity for I-Eb molecules by pigeon cytochrome c peptides compared with moth cytochrome c peptides, strongly argue that the immune response defect in the B10.A(5R) strain is due to a defect in Ag presentation (determinant selection). In contrast, B10.A and B10.S(9R) strains are high responders to pigeon cytochrome c. Both strains produce T cell clones which are capable of responding to cytochrome c presented by either B10.A or B10.S(9R) APC in vitro. We show that, even in T cells with this MHC restriction degeneracy, the TCR expressed in the two strains are different. Because the APC of both strains can clearly present the cytochrome c Ag, we conclude that the differential expression of the TCR in the responses is due to a T cell repertoire selection difference in the two strains. Thus, for the response to one Ag in three MHC congenic strains, there exists evidence that both determinant selection and repertoire selection can be mechanisms of Ir gene control of an immune response.
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PMID:Two distinct mechanisms account for the immune response (Ir) gene control of the T cell response to pigeon cytochrome c. 245 67

Two lines of evidence in the current study indicate that antigen processing is a major factor, in addition to MHC binding and T cell repertoire, that determines Ir gene responsiveness and epitope immunodominance. First, immunization with synthetic peptides of myoglobin sequences revealed new reactivities that had not appeared after priming with native myoglobin. For example, B10.S mice (H-2S) immune to equine myoglobin predominantly responded to peptide 102-118, whereas there was little, if any, response to this peptide in B10.BR (H-2k) mice immunized with native equine myoglobin. However, after immunization with the 102-118 peptide, both strains responded to the peptide. After in vitro restimulation, B10.BR T cells responded as well as B10.S T cells. Similarly, some individual 102-118-specific T cell clones from mice of both haplotypes showed similar dose responses and fine specificity patterns. Thus, low responsiveness to this site is due neither to a hole in the repertoire nor to a failure to bind to the appropriate MHC molecule. An alternative explanation was suggested by the observation that, whereas B10.S T cells from peptide 102-118-immune mice responded almost as well to whole myoglobin as to the peptide, the B10.BR T cells from peptide immune mice, while responding well to peptide, were poorly stimulated by whole myoglobin. Thus, the product of natural processing of equine myoglobin probably has hindering structures in the regions flanking the core epitope 102-118 that interfere with presentation by I-Ak but not I-AS. The second line of evidence that processing of native myoglobin may influence the apparent specificity of the T cell response was obtained using the I-Ad-restricted sperm whale myoglobin 102-118-specific clone 9.27. This clone discriminated readily between whole sperm whale myoglobin and equine myoglobin, but it did not distinguish between peptides corresponding to 102-118 of the sperm whale and equine sequences. This distinction between equine peptide and native equine myoglobin could be overcome by artificial "processing" of equine myoglobin with cyanogen bromide. In both sets of experiments, F1 APCs that present the same epitope well to T cells of another haplotype failed to overcome the defect, which was therefore not due to the availability of different processed cleavage fragments in APC of different haplotypes, as would be expected if there were MHC-linked processing. Thus, the differential responses to peptides versus native molecule for both I-Ad- and I-Ak-restricted clones appeared to depend on the restricting molecule used.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Influences of antigen processing on the expression of the T cell repertoire. Evidence for MHC-specific hindering structures on the products of processing. 245 73

Th cell-mediated rapid recognition of foreign Ag and the Ia molecule was studied using azobenzenearsonate-L-tyrosine (ABA-L-tyrosine)-specific Th cells (I-Ak restricted), foreign Ag (ABA-L-tyrosine), and APC (H-2k). Initial transmembrane signals in Th cell hybridomas (2-45-12) and in Th cell lines (A24-17 or A33-7) were monitored by stopped-flow fluorometry with fluorescent probes. It was found that Th cells recognized foreign Ag within 1 s at 25 degrees C on the APC (B10.BR spleen cells or L cells into which I-Ak genes were transferred). Recognition of foreign Ag and the Ia molecule was shown to deliver the initial signals to Th cell hybridomas and T cell lines. First, Th cells had membrane fluidity increased and then calcium was transported from the external medium into the T cells. The initial transmembrane signals to Th cell hybridomas were inhibited by the addition of an anti-I-Ak mAb. None of the initial signals were observed in the absence of either specific foreign Ag or APC.
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PMID:T cell-mediated recognition of foreign antigen and the Ia molecule observed by stopped-flow fluorometry. 245 16

Nase-specific T cell recognize the 86-100 peptide in association with B10.A APC. Clone N40 recognizes the 86-100 peptide in association with B10.A (Ek alpha Ek beta) and B10.A (5R) (Ek alpha Eb beta) APCs. We demonstrate here that a single amino acid substitution in the staphylococcal nuclease protein alters the structure of the processed peptide such that the T cell epitope recognized by clone N40 was only available for recognition in conjunction with B10.A (5R) but not the B10.A APCs. Other Nase-specific T cells recognize the mutant nuclease, and a synthetic peptide corresponding to the immunodominant region of the mutant protein was stimulatory for all the Nase-specific T cells. These results suggest that the mutation either affects the processing of the protein into antigenic peptides or affects the conformation of the processed fragment differently from that of the peptide.
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PMID:A single amino acid mutation in a protein antigen abrogates presentation of certain T cell determinants. 247 8


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