Nondominant CD8 T cells are active players in the vaccine-induced antitumor immune response.
J Immunol
; 186(7): 3847-57, 2011 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-21346233
ABSTRACT
We previously reported that CD8(+) T cells are directed predominantly toward the immunodominant Her-2/neu (neu) epitope RNEU(420-429) in nontolerized FVB/N but not tolerized HER-2/neu (neu-N) mice. In this study, we screened overlapping peptides of the entire neu protein and identified six new epitopes recognized by vaccine-induced neu-N-derived T cells. Evaluation of individual nondominant responses by tetramer staining and IFN-γ secretion demonstrate that this repertoire is peripherally tolerized. To address the role that the complete CD8(+) T cell repertoire plays in vaccine-induced antitumor immunity, we created a whole-cell vaccine-expressing neu cDNA that has been mutated at the RNEU(420-429) anchor residue, thereby abrogating activation of immunodominant epitope responses. Studies comparing the mutated and nonmutated vaccines indicate that nondominant CD8(+) T cells can induce antitumor immunity when combined with regulatory T cell-depleting agents in both neu-N and FVB/N mice. Collectively, these studies demonstrate that the neu-directed T cell repertoire is not intrinsically incapable of eradicating tumors. Rather, they are suppressed by mechanisms of peripheral tolerance. Thus, these studies provide new insights into the function of the complete T cell repertoire directed toward a clinically relevant tumor Ag in tumor-bearing hosts.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Epitopos Imunodominantes
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Receptor ErbB-2
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Linfócitos T CD8-Positivos
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Epitopos de Linfócito T
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Vacinas Anticâncer
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Neoplasias Mamárias Experimentais
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos