Consequences of suboptimal priming are apparent for low-avidity T-cell responses.

Abstract

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.

• Authors: Vanessa Venturi, Miles P Davenport, Natasha G Swan, Peter C Doherty, Katherine Kedzierska
• Journal: Immunology and cell biology (Immunol Cell Biol) Vol. 90 Issue 2 Pg. 216-23 (Feb 2012) ISSN: 1440-1711 [Electronic] United States
• PMID: 21556018 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Epitopes, T-Lymphocyte
• Receptors, Antigen, T-Cell

Topics

• Administration, Intranasal (methods)
• Animals
• CD8-Positive T-Lymphocytes (immunology)
• Epitopes, T-Lymphocyte (immunology)
• Influenza A Virus, H1N1 Subtype (genetics, immunology)
• Injections, Intraperitoneal (methods)
• Lymphocyte Activation (immunology)
• Mice
• Mice, Inbred C57BL
• Mutation
• Orthomyxoviridae Infections (genetics, immunology, virology)
• Receptors, Antigen, T-Cell (genetics, immunology)