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

Brenna J. Hill, Patricia A. Darrah, Zachary Ende, David R. Ambrozak, Kylie M. Quinn, Sam Darko, Emma Gostick, Linda Wooldridge, Hugo A. Van Den Berg, Vanessa Venturi, Martin Larsen, Miles P. Davenport, Robert A. Seder, David A. Price*, Daniel C. Douek

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

7 Citations (Scopus)

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 epitopespecific 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.

Original languageEnglish
Pages (from-to)5626-5636
Number of pages11
JournalJournal of Immunology
Volume193
Issue number11
DOIs
Publication statusPublished - 1 Dec 2014

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