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

Honda, Mitsuo, Wang, Rui, Kong, Wing-Pui, Kanekiyo, Masaru, Akahata, Wataru, Xu, Ling, Matsuo, Kazuhiro, Natarajan, Kannan, Robinson, Howard, Asher, Tedi E., Price, David ORCID: https://orcid.org/0000-0001-9416-2737, Douek, Daniel C., Margulies, David H. and Nabel, Gary J. 2009. Different vaccine vectors delivering the same antigen elicit CD8+ T cell responses with distinct clonotype and epitope specificity. The Journal of Immunology 183 (4) , pp. 2425-2434. 10.4049/jimmunol.0900581

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QR Microbiology > QR180 Immunology
Publisher:	American Association of Immunologists
ISSN:	0022-1767
Last Modified:	20 Oct 2022 08:47
URI:	https://orca.cardiff.ac.uk/id/eprint/29600

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