Selective identification of HLA-DP4 binding T cell epitopes encoded by the MAGE-A gene family

Autor: Bernard Lethe, Pierre van der Bruggen, Sandra Pouvelle-Moratille, Xiaofei Wang, Dominique Charron, Marc Busson, Hassan M. Zarour, William M. Cohen, Gaetan Munier, Florence Castelli, Christine Almunia, André Ménez, Bernard Maillere
Rok vydání: 2006
Předmět:
Zdroj: Cancer Immunology, Immunotherapy. 56:807-818
ISSN: 1432-0851
0340-7004
Popis: 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.
Databáze: OpenAIRE