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Preferential HLA Usage in the Influenza Virus-Specific CTL Response¹

Adrianus C. M. Boon^*, Gerrie de Mutsert^*, Ron A. M. Fouchier^*, Kees Sintnicolaas, Albert D. M. E. Osterhaus^* and Guus F. Rimmelzwaan^2,*

^* Department of Virology and World Health Organization National Influenza Center, Erasmus Medical Center, Rotterdam, The Netherlands; and Sanquin Bloodbank Rotterdam, Laboratory for Histocompatibility and Immunogenetics, Dordrecht, The Netherlands

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.

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