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.