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.

Abstract

Human cytotoxic T[thymus-derived]-cell responses are compared to 2 closely related viruses (type A and type B influenza) to study the antigen [Ag]-specific elements involved in HLA-linked genetic control of cytotoxic T cell responses. The HLA Ag function as self Ag that are recognized by cytotoxic T cells sensitized against either virus. However, in an informative family the HLA Ag preferentially recognized in conjunction with type A influenza (A/HK) apparently differ from the HLA Ag preferentially recognized in conjunction with type B influenza (B/HK). 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. HLA-linked regulation must operate by a mechanism(s) that is specific for the self HLA Ag and the viral Ag. Different HLA Ag may facilitate T cell responses to different pathogens, which would result in an evolutionary advantage for HLA heterozygosity.