Minimal tolerance to a tumor antigen encoded by a cancer-germline gene
(2012) Journal of Immunology — Vol. 188, n° 1, p. 111-121 (2012)
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- Abstract
- 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-Vβ 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.
- Affiliations
Université de la Méditerranée, Marseille, France CIML, UMR6546, Marseille, France; INSERM, UMR631, Marseille, France & CNRS, UMR6102, Marseille, France
Citations
Huijbers, I., Soudja, S. M., Uyttenhove, C., Buferne, M., Inderberg-Suso, E.-M., Colau, D., Pilotte, L., Powis de Tenbossche, C., Chomez, P., Brasseur, F., Schmitt-Verhulst, A.-M., & Van den Eynde, B. (2012). Minimal tolerance to a tumor antigen encoded by a cancer-germline gene. Journal of Immunology, 188(1), 111-121. https://doi.org/10.4049/jimmunol.1002612 (Original work published 2012)