Different vaccine vectors delivering the same antigen elicit CD8 + T cell responses with distinct clonotype and epitope specificity

Mitsuo Honda, Rui Wang, Wing Pui Kong, Masaru Kanekiyo, Wataru Akahata, Ling Xu, Kazuhiro Matsuo, Kannan Natarajan, Howard Robinson, Tedi E. Asher, David A. Price, Daniel C. Douek, David H. Margulies, Gary J. Nabel

Research output: Contribution to journalArticle

Abstract

Prime-boost immunization with gene-based vectors has been developed to generate more effective vaccines for AIDS, malaria, and tuberculosis. Although these vectors elicit potent T cell responses, the mechanisms by which they stimulate immunity are not well understood. In this study, we show that immunization by a single gene product, HIV-1 envelope, with alternative vector combinations elicits CD8+ cells with different fine specificities and kinetics of mobilization. Vaccine-induced CD8+ T cells recognized overlapping third V region loop peptides. Unexpectedly, two anchor variants bound H-2Dd better than the native sequences, and clones with distinct specificities were elicited by alternative vectors. X-ray crystallography revealed major differences in solvent exposure of MHC-bound peptide epitopes, suggesting that processed HIV-1 envelope gave rise to MHC-I/peptide conformations recognized by distinct CD8+ T cell populations. These findings suggest that different gene-based vectors generate peptides with alternative conformations within MHC-I that elicit distinct T cell responses after vaccination.

Original languageEnglish (US)
Pages (from-to)2425-2434
Number of pages10
JournalJournal of Immunology
Volume183
Issue number4
DOIs
StatePublished - Aug 15 2009
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

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    Honda, M., Wang, R., Kong, W. P., Kanekiyo, M., Akahata, W., Xu, L., Matsuo, K., Natarajan, K., Robinson, H., Asher, T. E., Price, D. A., Douek, D. C., Margulies, D. H., & Nabel, G. J. (2009). Different vaccine vectors delivering the same antigen elicit CD8 + T cell responses with distinct clonotype and epitope specificity. Journal of Immunology, 183(4), 2425-2434. https://doi.org/10.4049/jimmunol.0900581