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 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.
Wang
Xiao-Fei
XF
Protein Engineering and Research Department, CEA-Saclay, 91191 Gif sur Yvette, France.
Cohen
William M
WM
Castelli
Florence A
FA
Almunia
Christine
C
Lethé
Bernard
B
Pouvelle-Moratille
Sandra
S
Munier
Gaetan
G
Charron
Dominique
D
Ménez
André
A
Zarour
Hassan M
HM
van der Bruggen
Pierre
P
Busson
Marc
M
Maillère
Bernard
B
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019556:COS Cells; D002522:Chlorocebus aethiops; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006682:HLA-DP Antigens / Q000276:immunology*; D059868:HLA-DP beta-Chains; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins / Q000276:immunology*
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C056284:HLA-DPw4 antigen; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins