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

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 ce...

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Bibliographic Details
Published in:Cancer Immunology, Immunotherapy Immunotherapy, 2007-06, Vol.56 (6), p.807-818
Main Authors: Wang, Xiao-Fei, Cohen, William M, Castelli, Florence A, Almunia, Christine, Lethé, Bernard, Pouvelle-Moratille, Sandra, Munier, Gaetan, Charron, Dominique, Ménez, André, Zarour, Hassan M, van der Bruggen, Pierre, Busson, Marc, Maillère, Bernard
Format: Article
Language:English
Subjects:
Animals
Antigens
Antigens, Neoplasm - immunology
Cancer
CD4-Positive T-Lymphocytes - immunology
Cells
Chlorocebus aethiops
Chromatography
COS Cells
Epitopes, T-Lymphocyte - immunology
HLA-DP Antigens - immunology
HLA-DP beta-Chains
Humans
Life Sciences
Lymphocyte Activation - immunology
Lymphocytes
Medical research
Melanoma
Melanoma-Specific Antigens
Neoplasm Proteins - immunology
Original
Peptides
Proteins
Vaccines
White people
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Summary: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.
ISSN:0340-7004
1432-0851
1365-2567
DOI:10.1007/s00262-006-0230-y