Different vaccine vectors delivering the same antigen elicit CD8+ T cell responses with distinct clonotype and epitope specificity.
J Immunol
; 183(4): 2425-34, 2009 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-19620307
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-2D(d) 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antígenos H-2
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Proteína gp120 do Envelope de HIV
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Vacinas contra a AIDS
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Linfócitos T CD8-Positivos
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Epitopos de Linfócito T
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article