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Characterization of antigenic peptides presented by HLA‐B44 molecules on tumor cells expressing the gene MAGE‐3
Author(s) -
Fleischhauer Katharina,
Fruci Doriana,
van Endert Peter,
Herman Jean,
Tanzarella Silvia,
Wallny HansJ.,
Coulie Pierre,
Bordig Claudio,
Traversari Catia
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19961127)68:5<622::aid-ijc12>3.0.co;2-3
Subject(s) - epitope , human leukocyte antigen , peptide , microbiology and biotechnology , cytotoxic t cell , peptide sequence , antigen , amino acid , biology , lymphoblast , antigen presentation , hla b , hla b antigens , chemistry , in vitro , gene , biochemistry , cell culture , genetics
The amino acid sequence of the protein encoded by the gene MAGE‐3 was screened for peptides containing the binding motif for HLA‐B44. Nine peptides were synthesized, and their binding affinity for HLA‐B*4402 and ‐B*4403 was analyzed in an HLA class I α‐chain refolding assay. Four peptides with binding affinity for HLA‐B*4403 were chosen for in vitro cytotoxic T‐lymphocyte induction assays using as antigen‐presenting cells peptide‐pulsed, autologous activated B lymphoblasts from a healthy, B*4403 + donor. Peptide‐specific effectors could be raised only against one peptide, M3‐167. Cytotoxic T lymphocytes specific for this peptide were also able to recognize melanoma cell lines expressing HLA‐B44 and the gene MAGE‐3 , strongly suggesting that M3‐167is a naturally processed MAGE‐3 ‐encoded epitope presented by HLA‐B44.M3‐167 is a 1 amino acid N‐terminal extension of M3‐168, a naturally processed epitope MAGE‐3 ‐encoded epitope presented by HLA‐A1 that has been previously described. TAP binding studies of these 2 peptides revealed that the TAP affinity of M3‐167 is about 9‐fold higher than that of M3‐168. M3‐167 or a longer precursor could be transported into the endoplasmatic reticulum, where it could be trimmed for presentation by HLA‐A1 or ‐B44 molecules. Taken together, our data suggest that M3‐167 could be an immunodominant peptide encoded by the gene MAGE‐3 . © 1996 Wiley‐Liss, Inc.