In the present study, the recognition of epitope variants of influenza A viruses by human CTL was investigated. To this end, human CD8(+) CTL clones, specific for natural variants of the HLA-B*3501-restricted epitope in the nucleoprotein (NP(418-426)), were generated. As determined in (51)Cr release assays and by flow cytometry with HLA-B*3501-peptide tetrameric complexes, CTL clones were found to be specific for epitopes within one subtype or cross-reactive with heterosubtypic variants of the epitope. Using eight natural variants of the epitope, positions in the 9-mer important for T cell recognition and involved in escape from CTL immunity were identified and visualized using multidimensional scaling. It was shown that positions 4 and 5 in the 9-mer epitope were important determinants of T cell specificity. The in vivo existence of CD8(+) cells cross-reactive with homo- and heterosubtypic variants of the epitope was further confirmed using polyclonal T cell populations obtained after stimulation of PBMC with different influenza A viruses. Based on the observed recognition patterns of the clonal and polyclonal T cell populations and serology, it is hypothesized that consecutive infections with influenza viruses containing different variants of the epitope select for cross-reactive T cells in vivo.

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hdl.handle.net/1765/10311
Journal of Immunology
Erasmus MC: University Medical Center Rotterdam

Boon, A.C.M, de Mutsert, G, van Baarle, D, Smith, D.J, Lapedes, A.S, Fouchier, R.A.M, … Osterhaus, A.D.M.E. (2004). Recognition of homo- and heterosubtypic variants of influenza A viruses by human CD8+ T lymphocytes. Journal of Immunology. Retrieved from http://hdl.handle.net/1765/10311