International Immunology, Vol. 13, No. 11, 1373-1381,
November 2001
© 2001 Japanese Society for Immunology
Influenza A antigen exposure selects dominant Vß17+ TCR in human CD8+ cytotoxic T cell responses
Department of Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK
1 Enteric and Respiratory Virus Laboratory, Central Public Health Laboratory, London NW9 5HT, UK
Correspondence to: T. M. Lawson
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 Vß17+ 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 V0ß17 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 Vß17+ cells did not abrogate specific cytotoxicity. In contrast following natural influenza A infection, TCR Vß17+ CTL dominated to the extent that only one of nine adult CTL lines retained any functional activity after in vitro depletion of Vß17+ CTL. These results suggest that the dominance of Vß17+ 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.
Keywords: affinity, cytotoxic T cell, human, influenza A, TCR
Transmitting editor: E. Simpson
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