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Consequences of suboptimal priming are apparent for low‐avidity T‐cell responses
Author(s) -
Venturi Vanessa,
Davenport Miles P,
Swan Natasha G,
Doherty Peter C,
Kedzierska Katherine
Publication year - 2012
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2011.36
Subject(s) - epitope , priming (agriculture) , avidity , biology , virology , immunodominance , t cell , cytotoxic t cell , influenza a virus , immunology , population , cd8 , virus , antigen , immune system , genetics , medicine , in vitro , botany , environmental health , germination
The emergence of the novel reassortant A(H1N1)‐2009 influenza virus highlighted the threat to the global population posed by an influenza pandemic. Pre‐existing CD8 + T‐cell immunity targeting conserved epitopes provides immune protection against newly emerging strains of influenza virus, when minimal antibody immunity exists. However, the occurrence of mutations within T‐cell antigenic peptides that enable the virus to evade T‐cell recognition constitutes a substantial issue for virus control and vaccine design. Recent evidence suggests that it might be feasible to elicit CD8 + T‐cell memory pools to common virus mutants by pre‐emptive vaccination. However, there is a need for a greater understanding of CD8 + T‐cell immunity towards commonly emerging mutants. The present analysis focuses on novel and immunodominant, although of low pMHC‐I avidity, CD8 + T‐cell responses directed at the mutant influenza D b NP 366 epitope, D b NPM6A, following different routes of infection. We used a C57BL/6J model of influenza to dissect the effectiveness of the natural intranasal (i.n.) versus intraperitoneal (i.p.) priming for generating functional CD8 + T cells towards the D b NPM6A epitope. In contrast to comparable CD8 + T‐cell responses directed at the wild‐type epitopes, D b NP 366 and D b PA 224 , we found that the priming route greatly affected the numbers, cytokine profiles and TCR repertoire of the responding CD8 + T cells directed at the D b NPM6A viral mutant. As the magnitude, polyfunctionality, and T‐cell repertoire diversity are potential determinants of the protective efficacy of CD8 + T‐cell responses, our data have implications for the development of vaccines to combat virus mutants.