Epitope specificity delimits the functional capabilities of vaccine-induced CD8 T cell populations.
J Immunol
; 193(11): 5626-36, 2014 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-25348625
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-2K(d) 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-2D(d) 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-2D(d) 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Epitopos Imunodominantes
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Vacinas contra a AIDS
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Linfócitos T CD8-Positivos
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Produtos do Gene gag do Vírus da Imunodeficiência Humana
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Produtos do Gene pol do Vírus da Imunodeficiência Humana
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2014
Tipo de documento:
Article