Journal
JOURNAL OF IMMUNOLOGY
Volume 188, Issue 1, Pages 111-121Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1002612
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Funding
- Ludwig Institute for Cancer Research
- INSERM
- Centre National de la Recherche Scientifique
- European Community [LSHC-CT-2006-518234]
- Institut National du Cancer
- Institut National du Cancer Programme des Canceropoles
- Association pour la Recherche sur le Cancer
- Fondation contre le Cancer (Belgium)
- Fonds J. Maisin (Belgium)
- Walloon Region (Programme d'excellence CIBLES)
- Fonds National de la Recherche Scientifique (Belgium)
- Belgian Program Interuniversity Poles of Attraction
- Fonds National de la Recherche Scientifique
- Fonds pour la Recherche dans l'Industrie et l'Agriculture (Belgium)
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Central tolerance toward tissue-restricted Ags is considered to rely on ectopic expression in the thymus, which was also observed for tumor Ags encoded by cancer-germline genes. It is unknown whether endogenous expression shapes the T cell repertoire against the latter Ags and explains their weak immunogenicity. We addressed this question using mouse cancer-germline gene P1A, which encodes antigenic peptide P1A(35-43) presented by H-2L(d). We made P1A-knockout (P1A-KO) mice and asked whether their anti-P1A(35-43) immune responses were stronger than those of wild-type mice and whether P1A-KO mice responded to other P1A epitopes, against which wild-type mice were tolerized. We observed that both types of mice mounted similar P1A(35-43)-specific CD8 T cell responses, although the frequency of P1A(35-43)-specific CD8 T cells generated in response to P1A-expressing tumors was slightly higher in P1A-KO mice. This higher reactivity allowed naive P1A-KO mice to reject spontaneously P1A-expressing tumors, which progressed in wild-type mice. TCR-V beta usage of P1A(35-43)-specific CD8 cells was slightly modified in P1A-KO mice. Peptide P1A(35-43) remained the only P1A epitope recognized by CD8 T cells in both types of mice, which also displayed similar thymic selection of a transgenic TCR recognizing P1A(35-43). These results indicate the existence of a minimal tolerance to an Ag encoded by a cancer-germline gene and suggest that its endogenous expression only slightly affects diversification of the T cell repertoire against this Ag. The Journal of Immunology, 2012, 188: 111-121.
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