Human cytotoxic T cell responses to trinitrophenyl hapten and influenza virus. Diversity of restriction antigens and specificity of HLA-linked genetic regulation.
This report compares both the HLA restriction patterns and Ir gene regulation of human in vitro T cell-mediated cytotoxic responses to the trinitrophenyl (TNP) hapten and the type A and B influenza viruses. Comparison of the restriction patterns of these cytotoxic responses indicates that A/HK and B/HK are recognized in conjunction with polymorphic HLA-A and -B self determinants, whereas TNP is recognized in association with a more complex spectrum of self determinants. These self determinants include polymorphic HLA-A and -B determinants, polymorphic non-HLA-A and -B determinants that probably include DR antigens, and non-polymorphic determinants that appear to be species specific. Analysis of the self determinants recognized by human T cells in conjunction with influenza virus demonstrates that (a) the antigens recognized by virus-immune T cells can be distinguished from the serologically defined HLA-A and -B antigenic determinants, and (b) there may be multiple self determinants on individual HLA-A molecules that T cells can recognize in conjunction with virus. The results of family studies indicate that donors' T cells often preferentially respond to virus (and to a lesser extent TNP) in conjunction with products of one parental HLA haplotype (haplotype preference). In the family study, three HLA-identical siblings preferentially recognize paternal HLA antigens in conjunction with A/HK, and maternal HLA antigens in conjunction with B/HK and TNP, which indicates antigen-specific HLA-lined genetic control. Population studies demonstrate virus-specific differences in the ability of donors to respond to selected self HLA-A and -B antigens in conjunction with virus. These differences may be controlled by Ir genes that are distinct from HLA-A and -B, because differences are observed in the response patterns of HLA-A- and -B-matched individuals.
D000956:Antigens, Viral / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D005809:Genes, Regulator; D006680:HLA Antigens / Q000235:genetics*; D006241:Haptens / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D009578:Nitrobenzenes / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014301:Trinitrobenzenes / Q000276:immunology*
D000956:Antigens, Viral; D000939:Epitopes; D006680:HLA Antigens; D006241:Haptens; D009578:Nitrobenzenes; D014301:Trinitrobenzenes