Influenza A antigen exposure selects dominant Vβ17+ TCR in human CD8+ cytotoxic T cell responses

Thomas M. Lawson, Stephen Man, Sheila Williams, Adrianus C.M. Boon, Maria Zambon, Leszek K. Borysiewicz

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37 Scopus citations


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 Vβ17+ 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 Vβ17 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 Vβ17+ cells did not abrogate specific cytotoxicity. In contrast following natural influenza A infection, TCR Vβ17+ CTL dominated to the extent that only one of nine adult CTL lines retained any functional activity after in vitro depletion of Vβ17+ CTL. These results suggest that the dominance of Vβ17+ 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.

Original languageEnglish
Pages (from-to)1373-1381
Number of pages9
JournalInternational Immunology
Issue number11
StatePublished - Jan 1 2001


  • Affinity
  • Cytotoxic T cell
  • Human
  • Influenza A
  • TCR


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