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 work has indicated the significance of IL-4- and IL-5-secreting allergen-specific human Th2 lymphocytes in the control of immune responses to allergens in atopic individuals. The precise allergenic epitopes that activate these allergen-specific Th2 cells are, however, hardly known. We analyzed the epitope-specificity of T lymphocytes specific for Der p II, one of the major allergens of house dust mite Dermatophagoides pteronyssinus. Using a panel of overlapping synthetic peptides that span the entire Der p II molecule, we could demonstrate that polyclonal Der p II-specific T cell lines prepared from the peripheral blood of five atopic patients can react with at least 10 different epitopes of the molecule. Each donor showed a different pattern of reactivity with the synthetic peptides, suggesting that Der p II contains multiple T cell epitopes that may differ from individual to individual. We studied the specificity of the T cell response to Der p II in more detail in one atopic patient using a short term polyclonal T cell line that strongly reacted to one single peptide (116-129) of the allergen. From this patient we established a panel of 11 Der p II-specific TLC. Ten TLC were of the CD3+ CD4+ phenotype and showed a high IL-4/IFN-gamma production ratio, whereas another TLC expressed CD3 and CD8 and failed to secrete substantial IL-4 and IFN-gamma. The use of at least four different TCR V beta gene segments was shown within this panel TLC. All TLC tested recognized the allergen in an HLA-DR1-restricted manner. Although this patient reacted to only one peptide on the polyclonal level, two T cell epitopes were identified on the clonal level by using synthetic peptides and autologous APC to stimulate the TLC. Combining data of CD4/CD8 expression, TCR V beta usage, and epitope specificity, at least six different types of Der p II-specific TLC could be identified within this patient. Binding of IgE to all synthetic peptides of Der p II is low and of low affinity, which may be of particular importance with respect to possible desensitization protocols using such peptides.
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PMID:T cell epitopes of house dust mite major allergen Der p II. 768 99

After BMT, donor T cells are activated which can display GvHD as well as GvL activities. In order to study this GvL-specific T-cell response in vitro, proliferative T-cell clones from post-BMT PBMCs were generated by stimulation with a patient's leukemic cells. One CD4+ T-cell clone (designated M-33) displayed strong proliferative activity against the patient's leukemic cells but not against the patient's EBV-LCLs. The induction of proliferation, however, appeared not to be leukemia specific. Detailed analysis of the reactivity patterns revealed that T-cell clone M-33 recognizes an as yet unknown nonpolymorphic determinant in the context of self HLA-DRw52, presented by all but one type of APC. T-cell clone M-33 proliferated upon stimulation by PB-MCs, freshly isolated B cells, monocytes, dendritic cells, leukemic B cells, and nonleukemic B-cell blasts; solely in vitro EBV-transformed B cells and in vivo EBV-infected B cells failed to induce proliferation of T-cell clone M-33. Neither surface expression of MHC or accessory molecules on the EBV cells nor suppression caused by the EBV-infected cells could explain their failure to stimulate T-cell clone M-33. We therefore hypothesize that the absence of the stimulatory capacity once the B cells are virally infected could be the result of competition for MHC class II binding of the Epstein-Barr viral peptides, thus affecting the postulated DRw52-restricted peptide for recognition by T-cell clone M-33.
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PMID:Epstein-Barr virus infection abrogates the stimulatory capacity of B cells to a major histocompatibility complex class-II-restricted proliferative T-cell clone. 774 17

The mechanisms causing nonresponsiveness to hepatitis B surface Ag (HBsAg) vaccines in humans remain largely unknown. The increased incidence of nonresponsiveness in subjects with HLA-DR3 or -DR7 haplotype suggests that immune response mechanisms governed by genes of the MHC are involved. It is conceivable that APC of nonresponders are defective in the presentation of HBsAg because they are unable to adequately take up, process, or present this Ag. To examine this hypothesis we have used PBMC from nonresponders to present recombinant particles containing S or PreS2-S sequences to HBsAg-specific T cell lines from haplo-identical responder vaccinees. The proliferative response of these lines was used to evaluate the efficacy of Ag presentation. Unfractionated PBMC from five DR2+ and six DR7+ nonresponders did not proliferate to HBsAg in vitro, whereas they vigorously proliferated upon stimulation with tetanus toxoid, thus ruling out the presence of a generalized immunodeficiency. All DR2(15)+ nonresponders were able to present hepatitis B envelope Ag to HBsAg-specific, DR1501-restricted T cells. PBMC from six DR7+ nonresponders were all able to present HBsAg to DR07-restricted T cell lines and PBMC from three DPw4+ nonresponders were able to present HBsAg to DP0402-restricted T cell lines. Additional experiments showed that PBMC from two nonresponders presented HBsAg equally well and sometimes better than PBMC from two partially HLA-matched high responders. We conclude that HLA-DR2+, -DR7+, and -DPw4+ nonresponder vaccinees are able to take up, process and present HBsAg to allogeneic, haplo-identical T cell lines in vitro.
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PMID:Nonresponders to hepatitis B vaccine can present envelope particles to T lymphocytes. 781 65

CD4+ T cell clones were generated to tetanus toxin or to two tetanus toxin-derived peptides p2 (AA 830-834) and p30 (AA 947-976). 11 of the 24 p30-specific clones reacted to shorter p30 subunits (p301 or p302), and only 14 of the p2 or p30-specific clones reacted with TT presented by EBV-transformed B cell lines (B-LCL). The p30-specific clones were HLA-DP4 restricted. In contrast to autologous B cell lines, the majority of allogeneic, but HLA-DP4-positive cell lines failed to present p30 to the specific clones. We concluded that T cell clones are highly specific and that both, small alterations of the peptide length as well as discrete differences of the HLA-molecule may abrogate recognition of the peptide HLA complex by T cells. Moreover, use of peptides as stimulators of T cells may recruit and activate T cells which fail the "original" peptide, derived from normal antigen processing. Clones could usually be maintained in culture for 4-6 months, but with the help of freezing and thawing some clones are now available for over 2 years and still specific. Comparison of different autologous antigen-presenting cells, namely B-LCL and activated MHC class II-positive T cells revealed that not all clones were able to mount a proliferative response to peptide presentation by T cells, while all clones proliferated to B cells as APC. If stimulated with peptide and B-LCL, the clone proliferating to T cells as APC (so-called T responder clones) secreted a broad spectrum of cytokines (Th0-like) and were easier to maintain in culture. In contrast, clones which were unable to proliferate to peptide presentation, so-called T-nonresponder clones, showed a more restricted cytokine pattern and elevated or very low IL4/IFN gamma ratio upon antigen specific stimulation. However, all clones secreted at least small amounts of IL2, IL4, IFN gamma and TNF alpha, if stimulated by PMA and ionomycin. Thus, both chemical and antigen-specific stimulations should be considered if T cell clones are classified as Th1 or Th2, whereby those clones, which secrete a limited cytokine pattern after antigen stimulation only, might be named Th1 or Th2 like clones, while clones which even after PMA/ionomycin do not secrete all cytokines, might represent "real" Th1 or Th2 clones.
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PMID:Peptide-induced T cell clones: specificity, MHC restriction, proliferation and cytokine pattern as a function of different stimulations. 787 53

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

The four members of the HLA-DR11 family of class II molecules vary only by three or fewer amino acids via dimorphisms among DR beta-chain residues 67, 71, and 86. However, they differ markedly in their abilities to induce proliferation of DR(alpha,beta 1*1101)-restricted, peptide-specific T cell clones. To dissect which DR11-variable residues, individually and in combination, mediate these functional differences, we used as APC transfectants expressing DR molecules with one of all possible permutations of DR11-variable sequences, including the four DR11 family members, and four additional DR11 variant mutants. The abilities of the wild-type or mutant molecules to present two distinct influenza peptide Ags, HA307-19 and HA128-45, to T cells was assessed in in vitro T cell proliferation assays. Of the naturally dimorphic DR11 positions, residue beta 71 variation significantly influenced the ability of DR11 molecules to present both peptides to DR(alpha,beta 1*1101)-restricted T cells. Residue beta 86 variation had relatively less influence than reported in several other DR and peptide systems. Residue beta 67 variation usually appeared irrelevant to T cell proliferation, but in two mutants led to unexpected T cell proliferation independent of nominal peptide Ag. Peptide binding, assessed by flow cytometry, was not found to be altered by any mutations that disrupted DR(alpha,beta 1*1101)-like presentation. These data indicate that residue beta 71 exerts a central role in influencing the functional differences among DR11 molecules, whereas the widely studied dimorphism of residue beta 86 is not as generally influential in DR11 as in other alleles.
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PMID:Individual effects of the DR11-variable beta-chain residues 67, 71, and 86 upon DR(alpha,beta 1*1101)-restricted, peptide-specific T cell proliferation. 798 58

We have investigated the ability of APC Class II molecules to bind and release exogenous peptides, two phenomena that are still poorly understood. In order to investigate the half-life of the complex of an exogenous peptide with DR molecules we have evaluated the uptake and release of the radiolabeled peptide 17-29-Tyr of influenza virus matrix protein (MA 17-29-Y) by a B-EBV cell line at different times and under different conditions. We have found that the kinetics of both binding and release of the peptide are very fast in living cells; using glutaraldehyde-fixed cells, the kinetics of the two phenomena are slow, closely resembling those observed with the same peptide and purified, immobilized DR molecules. As confirmed by the study of a specific T-cell clone activation, the Class II-MA 17-29-Y complexes are short-living ones, with an average half-life of 55 min, and the DR molecules that bind exogenous peptides continuously undergo peptidic exchange. These data, taken together, suggest that the APC are endowed with cellular mechanisms that increase the efficiency of both the loading and the unloading of Class II HLA with exogenous peptides. These mechanisms do not appear to require ATP or to involve newly synthesized Class II molecules, intracellular acidic compartments, or the microtubule-microfilament system. On the other hand, an undamaged cell membrane appears to be crucial for an efficient binding.
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PMID:Cellular mechanisms of exogenous peptide binding to HLA class II molecules in B cells. 816 38

The natural Ag influenza virus A was used to test the requirements for the HLA-DR1-restricted presentation of the epitopes 18-29 in the matrix protein and 307-318 in the hemagglutinin protein. CD4+ cytotoxic T cell clones of similar efficiency were used to detect presentation of these two epitopes. Presentation of the matrix epitope by APC pulsed with either inactivated virus particles or purified soluble protein followed the classical pathway in that 1) it required invariant chain expression, 2) it was blocked by inhibition of protein synthesis, and 3) it was dependent on a function(s) encoded in the MHC class II region. These characteristics suggest that peptides corresponding to the matrix epitope can only load onto newly synthesized class II molecules that were targeted to a processing compartment by the invariant chain. In contrast, presentation of the hemagglutinin epitope processed from virus particles followed a different pathway. First, presentation of hemagglutinin was independent of invariant chain expression. Second, a human B lymphoblastoid cell line in which protein synthesis was inhibited for 9 h was still able to present hemagglutinin even at very low doses of Ag. Third, a DR1-transfected mutant B cell line missing the MHC class II region was able to present hemagglutinin. Thus, mature class II alpha beta molecules can acquire immunogenic peptides derived from intact natural Ags for presentation to CD4+ T cells. This pathway may be useful for the binding of peptides derived from Ags that are rapidly degraded upon uptake into APC.
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PMID:Two processing pathways for the MHC class II-restricted presentation of exogenous influenza virus antigen. 817 8

Our recent study indicated that all the insulin autoimmune syndrome (IAS) patients had specific HLA class II alleles, the DRB1*0406, DQA1*0301, and DQB1*0302, which allowed T cells to proliferate when autologous APC were exposed to human insulin. The study implied that gene products of DRB1*0406, DQA1*0301, and/or DQB1*0302 may be involved in the presentation of human insulin to T cells. We therefore examined T cell response of healthy donors with different HLA phenotypes to human insulin using an autologous MLR system. The T cells from not only IAS patients but also healthy donors were able to proliferate after exposure of human insulin to autologous APC with DRB1*0406, DQA1*0301, and DQB1*0302 products. The class II molecules are considered to be involved in the recognition of human insulin by T cells. The proliferative response of T cells was completely blocked by anti-HLA-DR mAb and not by anti-HLA-DQ mAb or other mAb. Furthermore, human insulin-specific CD4-positive T cell clones were established from blast cells in autologous MLR of PBMC from two healthy donors with DRB1*0406 in the presence of human insulin. Using DRB1*0406-transfected L cells as APC, we confirmed that these T cells clones recognize human insulin in the context of gene products of DRB1*0406. These results provide the first evidence that HLA-DRB1*0406 products act as the dominant restriction element for the presentation of human insulin to T cells, and suggest that this particular class II gene, HLA-DRB1*0406, contributes to the development of IAS.
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PMID:Recognition of human insulin in the context of HLA-DRB1*0406 products by T cells of insulin autoimmune syndrome patients and healthy donors. 822 61

The efficiency of stored platelet transfusion was evaluated in terms of clinical status in 136 thrombocytopenic patients. In a paired prospective study in which fresh platelets were used as controls, clinical efficiency was assessed on the basis of the ability to increase platelet count (recovery) and the interval to the next transfusion (D). In 48 clinically stable patients, recovery of fresh and stored platelets was similar (47% and 41% respectively) and the interval to the next transfusion was D4 and D3. In contrast, 27 patients who had bacterial infections showed significantly different recoveries (24%/5%) and the interval to the next transfusion was D3/D1 for fresh and stored platelets respectively. Similarly, in 16 patients who were treated concurrently with Amphotericin B, 18 other patients with graft-versus-host disease, 5 with splenomegaly and 3 with veno-occlusive disease (VOD), fresh platelets performed better than stored platelets, showing recoveries of 27%/18%, 29%/15%, 15%/1%, 22%/3%. Furthermore, the need for retransfusion within 24 hours was significantly increased with stored platelets. In 19 patients with anti-HLA allo-immunization who were transfused with HLA-matched fresh and stored APC, efficiency was similar (38%/36% and D4/D3). This study indicates that the storage has a major detrimental effect on platelet recovery and survival in patients with certain clinical conditions.
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PMID:[Influence of clinical status on the efficacy of stored platelet transfusion]. 825 53


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