Preferential HLA usage in the influenza virus-specific CTL response

To study whether individual HLA class I alleles are used preferentially or equally in human virus-specific CTL responses, the contribution of individual HLA-A and-B alleles to the human influenza virus-specific CTL response was investigated. To this end, PBMC were obtained from three groups of HLA-A and-B identical blood donors and stimulated with influenza virus. In the virus-specific CD8 T cell population, the proportion of IFN-- and TNF--producing cells, restricted by individual HLA-A and-B alleles, was determined using virus-infected C1R cells expressing a single HLA-A or-B allele for restimulation of these cells. In HLA-B*2705- and HLA-B*3501-positive individuals, these alleles were preferentially used in the influenza A virus-specific CTL response, while the contribution of HLA-B*0801 and HLA-A*0101 was minor in these donors. The magnitude of the HLA-B*0801-restricted response was even lower in the presence of HLA-B*2705. C1R cells expressing HLA-B*2705, HLA-A*0101, or HLA-A*0201 were preferentially lysed by virus-specific CD8 T cells. In contrast, the CTL response to influenza B virus was mainly directed toward HLA-B*0801-restricted epitopes. Thus, the preferential use of HLA alleles depended on the virus studied. The Journal of Immunology, 2004, 172: 4435–4443. C ytotoxic T lymphocytes have been shown to play an im-portant role in the control and clearance of virus infec-tions, including those caused by influenza virus (1, 2). Although a large number of peptides are generated during process-ing of viral proteins in infected cells, only some of these peptides are ultimately presented by MHC class I molecules and recognized by specific CTL. This limited recognition of a small number o