We have used antigen-specific human T-cell clones to study the relationship between MHC and antigen recognition specificities expressed by T cells. Tetanus toxoid (TT)-specific T-lymphocyte clones were derived from a immunized HLA-DR2,7 heterozygous donor by limiting dilution from peripheral blood mononuclear cells (PBM) restimulated with TT in vitro. Clones were screened for MHC-restricted antigen recognition against antigen-presenting cells (APC) from a panel of HLA-typed donors, using an in vitro T-cell proliferation assay. Several distinct patterns of antigen recognition were identified. In addition to T cells that recognized TT in association with donor class II MHC antigens, we found clones that simultaneously expressed self-restricted antigen recognition and alloreactivity, and clones with specificity for antigen in the context of MHC antigens not expressed by the T-cell donor. This was confirmed in inhibition studies using well-characterized monoclonal antibodies against class II MHC antigens to block specific proliferative responses. We propose a possible structure for the determinant recognized by two of the clones. These results suggest that the T-cell antigen receptor undergoes random or antigen-dependent changes in vitro, and that this may be a mechanism for somatic diversification of the T-cell repertoire.
Major histocompatibility complex (MHC) restricted antigen recognition: High frequency of human T-cell clones recognizing novel MHC class II determinants
주요 조직 적합성 복합체(MHC) 제한 항원 인식: 새로운 MHC 클래스 II 결정체를 인식하는 인간 T 세포 클론의 높은 빈도.
[Category] 파상풍,
[Article Type] journal-article
[Source] pubmed
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