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.

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.