Human cytotoxic T-cell responses to type A and type B influenza viruses can be restricted by different HLA antigens. Implications for HLA polymorphism and genetic regulation.
The present study compares human cytotoxic T-cell responses to two closely related viruses (type A and type B influenza) to understand the antigen-specific elements involved in HLA-linked genetic control of cytotoxic T-cell responses. The HLA antigens function as self antigens that are recognized by cytotoxic T cells sensitized against either virus. However, studies in an informative family indicate that in this family, the HLA antigens preferentially recognized in conjunction with type A influenza (A/HK) differ from the HLA antigens preferentially recognized in conjunction with type B influenza (B/HK). Similarly, population studies demonstrate that some (but not all) donors whose T cells recognized A/HK in conjunction with HLA-A2 failed to recognize B/HK in conjunction with HLA-A2. Thus, HLA-linked regulation must operate by a mechanism(s) that is specific both for the self HLA antigen and the viral antigen. Furthermore, these findings indicate that different HLA antigens may facilitate T-cell responses to different pathogens, which would result in an evolutionary advantage for HLA heterozygosity.
D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D006680:HLA Antigens; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D008297:Male; D009975:Orthomyxoviridae / Q000276:immunology*; D011110:Polymorphism, Genetic; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D006680:HLA Antigens