Influenza A antigen exposure selects dominant Vβ17+ TCR in human CD8+ cytotoxic T cell responses
Influenza A antigen exposure selects dominant Vβ17+ TCR in human CD8+ cytotoxic T cell responses
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DOI：
10.1093/intimm/13.11.1373
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发表时间：
2001-11-01
影响因子：
4.4
通讯作者：
Borysiewicz, LK
中科院分区：
文献类型：
--
作者：
Lawson, TM;Man, S;Borysiewicz, LK
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 (M1(58-66)) 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 V(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 M1(58-66)-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 M1(58-66)-specific CTL results from maturation and focussing of the response driven by exposure to influenza, and have implications for optimum immunization strategies.
