1. Selective identification of HLA-DP4 binding T cell epitopes encoded by the MAGE-A gene family.
- Author
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Wang XF, Cohen WM, Castelli FA, Almunia C, Lethé B, Pouvelle-Moratille S, Munier G, Charron D, Ménez A, Zarour HM, van der Bruggen P, Busson M, and Maillère B
- Subjects
- Animals, CD4-Positive T-Lymphocytes immunology, COS Cells, Chlorocebus aethiops, HLA-DP beta-Chains, Humans, Lymphocyte Activation immunology, Melanoma-Specific Antigens, Antigens, Neoplasm immunology, Epitopes, T-Lymphocyte immunology, HLA-DP Antigens immunology, Neoplasm Proteins immunology
- Abstract
Because of the high frequency of HLA-DP4 in the Caucasian population, we have selectively delineated HLA-DP4 restricted T cell epitopes in the MAGE-A tumor antigens. We identified 12 good binders to HLA-DP4 and investigated the capacity of the seven best binders to induce in vitro specific CD4+ T cell lines from HLA-DP4 healthy donors. We found that the MAGE-A1 90-104 peptide exhibited a high and constant frequency of CD4+ T cell precursors in all the six tested donors. The MAGE-A1 268-282 peptide was found immunogenic in only two donors but with a high precursor frequency. The MAGE-A12 127-141 peptide was T cell stimulating in six different donors and induced fewer T cell lines. The peptide-specific T cell lines were stimulated by DC loaded with the lysates of cells transfected with MAGE-A1 or MAGE-A12, or loaded with the recombinant protein. We also show that the immunoreactivity of CD4+ T cell epitopes restricted to the same HLA II molecule may vary from one individual to another, as a result of inter-individual variations in the CD4+ T cell repertoire.
- Published
- 2007
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