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T N Schumacher M L De Bruijn L N Vernie W M Kast C J Melief J J Neefjes H L Ploegh 《Nature》1991,350(6320):703-706
Synthetic peptides have been used to sensitize target cells and thereby screen for epitopes recognized by T cells. Most epitopes of cytotoxic T lymphocytes can be mimicked by synthetic peptides of 12-15 amino acids. Although in specific cases, truncations of peptides improves sensitization of target cells, no optimum length for binding to major histocompatibility complex (MHC) class I molecules has been defined. We have now analysed synthetic peptide captured by empty MHC class I molecules of the mutant cell line RMA-S. We found that class I molecules preferentially bound short peptides (nine amino acids) and selectively bound these peptides even when they were a minor component in a mixture of longer peptides. These results may help to explain the difference in size restriction of T-cell epitopes between experiments with synthetic peptides and those with naturally processed peptides. 相似文献
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T cell depletion in transgenic mice carrying a mutant gene for TCR-beta 总被引:12,自引:0,他引:12
Classical T lymphocytes recognize foreign antigens in the context of self major histocompatibility complex (MHC) molecules by means of the T-cell receptor (TCR)alpha beta heterodimer. The genes for TCR beta-chains, like immunoglobulin genes, are subject to allelic exclusion. The introduction of a functional TCR-beta gene into the germline of mice prevents rearrangement of endogenous TCR-beta genes. Here we report that the introduction of a non-functional TCR-beta genes. Here we report that the introduction of a non-functional TCR-beta gene with a deletion of the major part of the variable region (delta V-TCR-beta), also inhibits endogenous TCR-beta gene rearrangement. This inhibition is mediated via the encoded protein because impairment of endogenous TCR-beta gene rearrangement is not found if a frameshift mutation is introduced into the DJ region of the delta V-TCR-beta transgene. The delta V-TCR-beta transgene can lead to two phenotypes, in which lymphoid development is perturbed. Phenotype A is characterized by a severe impairment of both T and B cell development as reflected by the complete absence of certain lymphoid organs. In phenotype B, lymphoid organs are macroscopically normal, but T cell differentiation is impeded. Virtually all thymocytes lack membrane expression of TCR-alpha beta, but nevertheless carry the CD4 and CD8 antigens (CD4+CD8+ phenotype); they do not, however, mature further. The defect in mice of phenotype B but not of phenotype A can be corrected by the introduction of a functional TCR-beta gene. 相似文献
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Murine cytotoxic T (Tc)-cell responses to various antigens are controlled by immune response (Ir) genes mapping in the major histocompatibility complex (H-2). The genes responsible are those encoding the class I and class II H-2 antigens. The H-2 I-Ab mutant mouse strain bm12 differs from its strain of origin, C57BL/6 (H-2b), only in three amino acids in the I-A beta bm12 class II H-2 molecule. As a consequence, female bm12 mice are Tc-cell nonresponders to the male antigen H-Y and do not reject H-Y disparate skin grafts. We now report that bm12 mice generate strong H-Y-specific Tc cells following priming in vivo and restimulation in vitro with male bm12 dendritic cells (DC). Female bm12 mice primed with male DC also reject male skin grafts. Furthermore, we demonstrate that only responder cell populations containing a mixture of L3T4+ (T-helper (Th) phenotype) and Lyt 2+ (Tc phenotype) T lymphocytes generate H-Y-specific Tc cells. These data imply an essential role for Th cells, activated by DC as antigen-presenting cells (APC), in changing H-Y-nonresponder bm12 mice into H-Y responders. Priming and restimulation with DC allows the triggering of a T-cell repertoire not demonstrable by the usual modes of immunization. This principle might be used to overcome other specific immune response defects. 相似文献
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J Borst R J van de Griend J W van Oostveen S L Ang C J Melief J G Seidman R L Bolhuis 《Nature》1987,325(6106):683-688
Cloned blood lymphocytes that do not express the alpha- and beta-chains of the T-cell receptor show MHC-unrestricted cytotoxicity. These cells carry the gamma-protein, disulphide-linked either to another molecule or to itself, and associated with the CD3 complex. These observations may help to solve the mystery posed by the discovery of the gamma gene. 相似文献
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