Epitope specificity delimits the functional capabilities of vaccine-induced CD8 T Cell populations

Hill, Brenna J., Darrah, Patricia A., Ende, Zachary, Ambrozak, David R., Quinn, Kylie M., Darko, Sam, Gostick, Emma, Wooldridge, Linda, van den Berg, Hugo A., Venturi, Vanessa, Larsen, Martin, Davenport, Miles P., Seder, Robert A., Price, David ORCID: https://orcid.org/0000-0001-9416-2737 and Douek, Daniel C. 2014. Epitope specificity delimits the functional capabilities of vaccine-induced CD8 T Cell populations. The Journal of Immunology 193 (11) , pp. 5626-5636. 10.4049/jimmunol.1401017

Full text not available from this repository.

Abstract

Despite progress toward understanding the correlates of protective T cell immunity in HIV infection, the optimal approach to Ag delivery by vaccination remains uncertain. We characterized two immunodominant CD8 T cell populations generated in response to immunization of BALB/c mice with a replication-deficient adenovirus serotype 5 vector expressing the HIV-derived Gag and Pol proteins at equivalent levels. The Gag-AI9/H-2Kd epitope elicited high-avidity CD8 T cell populations with architecturally diverse clonotypic repertoires that displayed potent lytic activity in vivo. In contrast, the Pol-LI9/H-2Dd epitope elicited motif-constrained CD8 T cell repertoires that displayed lower levels of physical avidity and lytic activity despite equivalent measures of overall clonality. Although low-dose vaccination enhanced the functional profiles of both epitope-specific CD8 T cell populations, greater polyfunctionality was apparent within the Pol-LI9/H-2Dd specificity. Higher proportions of central memory-like cells were present after low-dose vaccination and at later time points. However, there were no noteworthy phenotypic differences between epitope-specific CD8 T cell populations across vaccine doses or time points. Collectively, these data indicate that the functional and phenotypic properties of vaccine-induced CD8 T cell populations are sensitive to dose manipulation, yet constrained by epitope specificity in a clonotype-dependent manner.

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
Date of Acceptance:	3 October 2014
Last Modified:	28 Oct 2022 10:31
URI:	https://orca.cardiff.ac.uk/id/eprint/78689

Citation Data

Cited 7 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item