Functional heterogeneity of HLA-A*02 subtypes revealed by presentation of a MAGE-3-encoded peptide to cytotoxic T cell clones.
The peptide-binding and presentation characteristics of seven naturally occurring HLA-A2 subtypes were studied using M3(271), a peptide derived from the tumor-specific Ag encoded by gene MAGE-3, which has been shown to be processed and presented by A*0201+ melanoma lines. Three independent M3(271)-specific CTL clones were obtained from two unrelated A*0201+ donors. B lymphoblastoid cell lines (BLCLs) expressing A*0201, A*0207, or A*0209 could be sensitized to lysis by all three clones upon incubation with the relevant peptide. Furthermore, the same BLCLs were able to present endogenous M3(271) in IFN-gamma release assays. These findings demonstrate, for the first time, the existence of a functional overlap between A*0207 and other A*02 subtypes. One of the CTL clones also lysed M3(271)-pulsed BLCLs expressing A*0204 and A*0206, while the other two clones recognized M3(271) only in the context of either of these two subtypes. Peptide-pulsed BLCLs expressing A*0202 or A*0205 were not lysed, although A*0205 and, with lower affinity, A*0202 molecules were shown to bind peptide M3(271). These findings have implications for the selection of cancer patients for specific immunotherapy with peptide M3(271).
Fleischhauer
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Telethon Institute of Gene Therapy, and Gene Therapy Program, Istituto Scientifico H.S. Raffaele, Milan, Italy. fleisck@tigem.it
Tanzarella
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Russo
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van der Bruggen
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Bordignon
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Traversari
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D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D002461:Cell Line, Transformed; D003602:Cytotoxicity, Immunologic; D015329:Gene Rearrangement, T-Lymphocyte; D015789:HLA-A2 Antigen / Q000145:classification / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D008545:Melanoma / Q000276:immunology*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000276:immunology*; D009369:Neoplasms / Q000628:therapy; D018579:Patient Selection; D010446:Peptide Fragments / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta