Influenza A antigen exposure selects dominant V[beta]17+ TCR in human CD8+ cytotoxic T cell responses.

Original Research Papers
International Immunology. 13(11):1373-1381, November 2001.
Lawson, Thomas M.; Man, Stephen; Williams, Sheila; Boon, Adrianus C. M. 1; Zambon, Maria 1; Borysiewicz, Leszek K.

During acute human viral infections, such as influenza A, specific cytotoxic T lymphocytes (CTL) are generated which aid virus clearance. We have observed that in HLA-A*0201+ subjects, CTL expressing V[beta]17+ TCR and recognizing a peptide from the influenza A matrix protein (M158-66) dominate this response. In experimental models of infection such dominance can be due to inheritance of a restricted T cell repertoire or acquired consequent on expansion of CTL bearing an optimum TCR conformation against the MHC-peptide complex. To examine how influenza A infection might influence the development of TCR V0[beta]17 expansion, we studied influenza A-specific CTL in a cross-sectional study of 82 HLA-A*0201+ individuals from birth (cord blood) to adulthood. Primary M158-66 -specific CTL were detected in cord blood, but their TCR were diverse and depletion of V[beta]17+ cells did not abrogate specific cytotoxicity. In contrast following natural influenza A infection, TCR V[beta]17+ CTL dominated to the extent that only one of nine adult CTL lines retained any functional activity after in vitro depletion of V[beta]17+ CTL. These results suggest that the dominance of V[beta]17+ TCR among adult M158-66-specific CTL results from maturation and focussing of the response driven by exposure to influenza, and have implications for optimum immunization strategies.


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