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
|
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: | Schools > Medicine Research Institutes & Centres > 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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