Multiple specificities in the repertoire of a melanoma patient's cytolytic T lymphocytes directed against tumor antigen MAGE-1.A1

doi:10.1084/jem.182.4.1019

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Multiple specificities in the repertoire of a melanoma patient's cytolytic T lymphocytes directed against tumor antigen MAGE-1.A1

P Romero, C Pannetier, J Herman, CV Jongeneel, JC Cerottini and PG Coulie
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland.

Peptide MAGE-1.A1 is a nonamer derived from protein MAGE-1 that can associate with the HLA-A1 molecule. It was shown previously to be recognized by an antitumor cytolytic T lymphocyte (CTL) clone derived from the blood of melanoma patient MZ2. We derived two other anti-MAGE- 1.A1 CTL clones from different blood samples of the same patient and compared the fine specificity of recognition of the three CTL by testing them on variant MAGE-1.A1 peptides incorporating different amino acid substitutions. The epitopes recognized by the CTL proved to be different. While modifications of residues at positions 5, 6, or 7 in the antigenic peptide affected recognition by the three CTL, each of the modifications 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 cell antigen receptor of the three CTL were completely different. The results indicate a long-lasting diversity in terms of fine specificity and 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.
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