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

T cell somatic hybrids were obtained by fusion of human tetanus toxoid-specific gamma + delta + T cells and a T cell lymphoma cell line that expresses beta-chain but not alpha-chain transcripts. The hybrids simultaneously and independently expressed alpha beta and gamma delta TCR heterodimers on the cell surface without any significant differences in the level of expression. No heterodimers containing alpha delta-, beta delta-, beta gamma-, and alpha gamma-chains were transported to the cell membrane, indicating a chain specificity in dimer formation. The presence of productively rearranged gamma- and delta-alleles in the hybrid cells and immunoprecipitation of an identical type of TCR-gamma delta from both hybrid and parental gamma + delta + T cells suggests that TCR-gamma delta on the hybrid cells derives from gamma + delta + T cells. Anti-TCR (TCS-delta 1 or WT31) and anti-CD3 antibodies induced a rapid increase in [Ca2+]i in the double-positive hybrids and their variants positive for either the alpha beta or gamma delta complex. Double positive hybrid cells were refractory to stimulation with anti-CD3 antibody after pretreatment with a mixture of anti-TCR-gamma delta and anti-TCR-alpha beta antibodies but not with either antibody alone indicating the functional independence of the two receptors. However, only gamma delta heterodimer receptor was able to respond to tetanus toxoid presented on autologous APC as measured by induction of the p55 chain of IL-2R on stimulated cells.
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PMID:Expression and function of gamma delta- and alpha beta-T cell receptor heterodimers on human somatic T cell hybrids. 169 58

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

Murine T cell hybridomas were used to examine the requirements for processing and presentation of human fibrinogen. In contrast to most protein Ag, fibrinogen (Mr 340,000) did not need to be processed by an APC, inasmuch as intact fibrinogen was presented by both pre-fixed and chloroquine-treated macrophages. Through the use of a variety of protease inhibitors, no involvement of proteases either on the macrophage surface or in the culture medium in the presentation of fibrinogen was observed. The epitope recognized by two T cell hybridomas was localized to the peptide, A alpha (551-578), which was located on the carboxy portion of the A alpha-chain. This portion of the A alpha-chain has no defined secondary structure and must possess the conformational flexibility which allows it to directly associate with an I-Ek molecule. Thus conformational flexibility may be a major factor in determining the processing requirements of a protein Ag.
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PMID:T cell recognition of fibrinogen. A determinant on the A alpha-chain does not require processing. 244 93

Class II-restricted murine T cell clones specific for the immunogenic determinant L-tyrosine-p-azobenzenearsonate failed to proliferate to Ag presented by L cell lines transfected with and expressing the appropriate class II genes, but are activated to kill the APC in an Ag-dependent, MHC-restricted manner. Inhibition of APC proliferation was used as an assay to determine the relative contributions of polymorphic sites on the class II alpha- and beta-chains to MHC-restricted activation of I-A beta k-restricted cloned T cells. Transfectants expressing A beta k in conjunction with the alpha chain of k, u, or d were equally effective APCs, whereas transfectants expressing A beta u were completely ineffective, implicating the beta-chain as more critical for the presentation of L-tyrosine-p-azobenzenearsonate. Site-directed mutagenesis of polymorphic positions in the beta chain revealed a remarkable stringency for the k haplotype, in contrast to the relaxed alpha-chain requirement. These results, in conjunction with others, indicate that the relative contribution of polymorphic sites on class II alpha- and beta-chains to T cell Ag recognition can differ markedly, and, furthermore, may vary as a function of the Ag.
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PMID:Arsonate-specific murine T cell clones. V. Antigen presentation by L cells transfected with normal and mutant class II genes. 247 38

Thymectomy of 3-day-old mice results in the development of multi-organ-specific autoimmune diseases. The disease process is mediated by CD4+ T cells and is characterized by an inflammatory infiltrate in the affected organ(s) and the presence of autoantibodies. Our analysis of the phenotype of the CD4+ T cells that remain in the 3-day thymectomized animal revealed that the majority (approximately 80%) of the CD4+ lymph node cells express an activated (MEL-14low) phenotype and a smaller percentage expressed the T cell activation Ag CD69 and IL-2R alpha-chain. Thymectomized animals also had an increase in the frequency of mitogen-induced CD4+ IL-4 producers and significantly higher levels of total serum IgG. Functional studies demonstrated that lymph node T cells from 3-day thymectomized mice had an enhanced response in the syngeneic MLR and appeared to preferentially respond to syngeneic dendritic cells. To determine whether the syngeneic MLR-reactive T cells were involved in the pathogenesis of the organ-specific disease, we developed a model that mimicked the 3dTx model by grafting neonatal thymi to adult nu/nu recipients followed by removal of the thymus graft on day 3 or 4. When compared with mice transplanted with an untreated thymus, nu/nu mice transplanted with adult APC-containing thymi demonstrated a decrease in the incidence and severity of gastritis, a marked decrease in the titer of anti-parietal cell Ab, and a decrease in total serum IgG. Thus, intrathymic tolerization to complexes of self-peptides and MHC class II on adult APC prevents organ-specific autoimmune disease.
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PMID:Pathogenesis of post-thymectomy autoimmunity. Role of syngeneic MLR-reactive T cells. 775 94

In these experiments, effects of IL-12 on the proliferation and IL-2R expression of Th1 and Th2 clones were studied. Although neither Th1 nor Th2 clones proliferated on an Ag stimulation with B cell APC, Th1 clones but not Th2 clones, exhibited IL-2-dependent proliferation in the presence of IL-12 in response to the Ag stimulation. The IL-2R alpha-chain was also shown to be induced on Th1 clones when they were stimulated with B cell APC in the presence of IL-12. Effects of IL-12 on these T cell functions were indicated to be exerted in concert with IL-2, although IL-12 did not enhance IL-2 production of Th1 clones. Cytokines produced by Th1 clones such as IFN-gamma and TNF-alpha were indicated not to be involved in induction of the IL-2R alpha-chain expression or proliferation. IL-12 also induced proliferation and IL-2R alpha-chain expression of Th1 clone stimulated with anti-CD3 in the absence of APC, indicating that IL-12 exerted the effect on Th1 cells directly and other costimulator signal from APC is not required for the function of IL-12. In contrast to IL-12, IL-1 induced proliferation and IL-2R alpha-chain expression of Th2 clones stimulated with Ag on B cell APC. The failure of IL-12 in the induction of IL-2R alpha-chain expression on Th2 clone seemed not to be caused by the IL-4 produced by the clone. These results suggest that IL-12 plays an important role in IL-2R alpha-chain expression and proliferation of Th1 clones, but not Th2 clones, as a second signal.
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PMID:Second signal activity of IL-12 on the proliferation and IL-2R expression of T helper cell-1 clone. 790 27

The initial event triggering the activation of Th cells occurs when the TCR interacts with antigenic peptide in the context of the MHC II on APC. Various T cell accessory molecules including CD4, CD28, and LFA-1 participate and facilitate the activation event. Although some evidence for the interaction of MHC II and CD4 is available, the site of MHC class II (alpha-chain, beta-chain, or both chains) for CD4 interaction has not yet been clearly defined. Results from different laboratories had indicated the involvement of alpha 1, beta 1, and beta 2 domains of MHC class II molecules in CD4 interaction. Recently, a conserved site of DR beta 2 domain has been identified that involves CD4 interaction that is analogous to MHC class I binding site for CD8 molecule. In this report, direct binding of affinity-purified HLA-DR2 dimer and its isolated alpha- and beta-chains to CD4 was studied using a CD4-transfected HeLa cell line. Preferential binding of the beta-chain and intact MHC II dimer to the CD4-transfected cells was observed and found to be specifically inhibited by anti-CD4 mAb. In contrast, the isolated alpha-chain of HLA DR2 did not show significant binding to CD4-transfected cells. Complexes of radiolabeled DR2 dimer or beta-chain alone with an immunodominant epitope from myelin basic protein (83-102) did not show any further increase in binding of these molecules. Binding of the beta-chain to CD4+ cells was markedly inhibited by a DR beta 1 peptide (35-46) and was partially inhibited by a DR beta 2 peptide (134-148) of MHC class II molecule. These results suggest the involvement of at least two conserved regions of the beta polypeptide chain of MHC class II in CD4 interaction. Because in our experiments transfected cells lack TCR molecules and the binding of DR2 to the CD4-transfected cells was unaffected by added antigenic peptide, it is possible that the interaction of MHC class II to CD4 is independent of TCR occupancy.
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PMID:Purified beta-chain of MHC class II binds to CD4 molecules on transfected HeLa cells. 843 82

Stimulation of OVA-specific suppressor T cell (Ts) hybridoma and bee venom phospholipase A2 (PLA2)-specific Ts hybridoma with Ag-pulsed APC or by cross-linking of CD3 resulted in the formation of Ag-specific glycosylation-inhibiting factor (GIF). Affinity-purified Ag-specific GIF preparations, obtained by using Ag-coupled Sepharose or anti-TCR alpha-chain-coupled Affi-Gel, contained a 55-kDa peptide, which bound both polyclonal anti-GIF Abs and anti-TCR-alpha mAb in immunoblotting. The same hybridomas constitutively secrete 13-kDa bioactive GIF peptide that has no affinity for homologous Ag, but neither the Ag-specific GIF activity nor 55-kDa GIF peptide was detectable in culture supernatants of unstimulated cells. Northern blot analysis of mRNA from the anti-CD3-stimulated hybridoma with 32P-labeled GIF cDNA revealed only 0.6 kb mRNA, which encodes the 13-kDa nonspecific GIF. No mRNA of the 55-kDa GIF was detectable. A representative OVA-specific Th hybridoma, DO 11.10 cells contain the 0.6 kb GIF mRNA and constitutively secrete inactive GIF peptide. However, the Th hybridoma failed to secrete the 55-kDa peptide or any peptide with the TCR-alpha determinant upon stimulation with anti-CD3. It appears that the formation of the 55-kDa peptide with the TCR-alpha determinant is unique for a subset of T cells including Ts cells that form bioactive GIF.
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PMID:Biochemical characterization of antigen-specific glycosylation-inhibiting factor from antigen-specific suppressor T cells. I. Identification of a 55-kilodalton glycosylation-inhibiting factor peptide with TCR alpha-chain determinant. 859 20

Residues 46 and 54 on pigeon cytochrome c 43-58 (p43-58) analogues function as agretopes (sites bound to MHC molecules). Phenylalanine (F) and alanine (A) at positions 46 and 54 on p43-58 respectively bind to I-Ab. Aspartic acid (D) and alanine at positions 46 and 54 respectively bind to I-Ak. To determine the allele specific binding sites (desetope (s)) on class II molecules that are correspondent to the agretopes of peptide antigen (Ag), we analyzed directly binding capacity of p43-58 analogues with glutamic acid (E) at the epitopic position 50 (50E) to L cell transfectants expressing recombinant I-A molecules between b and k types. An Ak binding peptide, 46D50E54A, bound to transfectant possessing amino acid sequence of k type on N-terminal half of alpha-helix of A alpha-chain irrespective of the b type sequence on the other part, whereas an Ab binding peptide, 46F50E54A, did not bind to these transfects. Thus, agretopic residue 46 of 46D50E54A peptides appeared to bind to N-terminal half of alpha-helix of A alpha-chain. To define critical residues for the allele specific peptide binding, we then analyzed peptide binding capacity of Ak mutants substituted one of four polymorphic residues between Ak and Ab molecules. An Ak mutant, Ak alpha(56A), where arginine (R) at position 56 of the Ak alpha-chains was substituted with alanine located at the same position 56 of the Ab alpha-chains hardly bound 46D50E54A. By contrast, the Ak alpha(56A) bound 46F50E54A. Furthermore, Ak restricted T cell hybridomas responded to 46F50E54A but not to 46D50E54A in the presence of the Ak alpha(56A) APC. Thus, an amino acid on the position 56 of A alpha-chain determines critically specificity of the allele specific peptide binding (desetope).
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PMID:[Analysis of the allele specific Ag-binding site on murine class II MHC]. 864 75

Regulation of experimental autoimmune encephalomyelitis (EAE) can be induced by anti-idiotype immunity against T cell receptor (TCR) fragments associated with major histocompatibility complex (MHC) molecules. However, we have recently found that preimmunization with an alpha-chain TCR CDR3 peptide (LYFCAARSNYQL) derived from myelin basic protein (MBP)-specific clones did not suppress but rather augmented the severity of EAE induced by MBP-specific T cells in SJL/J mice. To test whether CDR3 vaccination could control only a highly restricted T cell population, we studied the effect of the peptide against EAE induced by T cells specific for different Ag/MHC ligands and autoimmune diseases affecting non-neural tissues. In contrast to expectations, the peptide was found to augment not only EAE induced by MBP-specific T cells, but also proteolipid protein (PLP)-specific T cell- or PLP peptide-induced EAE in SJL/J mice, and MBP-induced EAE and adjuvant arthritis (AA) in rats. The CDR3 peptide was neither inhibitory nor supportive for Ag-induced activation of an encephalitogenic clone in vitro. In addition, the peptide treatment neither inhibited the induction of Ag-specific T cells nor altered the APC function of spleen cells. These findings, on the one hand, confirm previous results showing TCR peptide-induced enhancement of the disease and, on the other hand, indicate that the TCR CDR3 peptide may control T cells with broader Ag/MHC specificities than could be expected. Structural similarity among TCR idiotypes of autoimmune T cells may partly account for these results.
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PMID:An alpha-chain TCR CDR3 peptide can enhance EAE induced by myelin basic protein or proteolipid protein. 889 82


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