MULTIPLE SPECIFICITIES IN THE REPERTOIRE OF A MELANOMA PATIENTS CYTOLYTIC T-LYMPHOCYTES DIRECTED AGAINST TUMOR-ANTIGEN MAGE-1.A1

Peptide MAGE-1.A1 is a nonamer derived from protein MAGE-1 that can as sociate with the HLA-A1 molecule. It was shown previously to be recogn ized by an antitumor cytolytic T lymphocyte (CTL) clone derived from t he blood of melanoma patient MZ2. We derived two other anti-MAGE-1.A1 CTL clones from different blood samples of the same patient and compar ed the fine specificity of recognition of the three CTL by testing the m on variant MAGE-1.A1 peptides incorporating different amino acid sub stitutions. The epitopes recognized by the CTL proved to be different. While modifications of residues at positions 5, 6, or 7 in the antige nic peptide affected recognition by the three CTL, each of the modific ations of residues at positions 1, 4, or 8 affected recognition by one CTL only. The sequences of both the alpha and beta chains of the T ce ll antigen receptor of the three CTL were completely different. The re sults indicate a long-lasting diversity in terms of fine specificity a nd of T cell antigen receptor structure in the repertoire of antitumor CTL derived from the blood of a melanoma patient and directed against a defined tumor antigen.