Major histocompatibility complex (MHC) restricted antigen recognition: high frequency of human T-cell clones recognizing novel MHC class II determinants.
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.
D000911:Antibodies, Monoclonal; D000938:Antigen-Presenting Cells / Q000276:immunology; D001667:Binding, Competitive; D002999:Clone Cells / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D015809:HLA-DR7 Antigen; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006684:HLA-DR Antigens; D015809:HLA-DR7 Antigen; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D013745:Tetanus Toxoid