Influenza virus-specific cytotoxic T cells are restricted by multiple HLA-A3-related self antigens: evidence for recognition of distinct self structures in conjunction with different foreign antigens.

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Abstract
In the experiments described in this report we examined the similarities and differences in target cell recognition by influenza-immune CTL that share HLA-A3 but no other defined HLA-A, -B, or -C specificity with each of a panel of virus-infected target cells. Virus-immune CTL populations obtained from selected HLA-A3-positive donors can distinguish between the virus-infected target cells of unrelated donors, as assessed by direct cytotoxicity and cold target inhibition. The CTL restriction antigens that are associated with HLA-A3 in the population are encoded by gene(s) that segregate with HLA-A3 in an HLA-A/C recombinant family. These results suggest that HLA-A3-positive cells from unrelated individuals may differ with respect to 1 or more individual CTL restriction antigens associated with their HLA-A3 molecules, and that each of these distinct restriction antigens is recognized by a different subpopulation of virus-immune CTL. Analysis of the self specificity of T cells from individual donors sensitized against 2 noncross-reacting viruses, type A and type B influenza, indicated that CTL can recognize different foreign antigens in conjunction with different HLA-A3-related self antigens. These results are consistent with a model that proposes that each HLA-A and -B molecule possesses multiple CTL restriction antigens, each of which may function as self recognition structures for CTL that respond to different foreign antigens.