ANALYSIS OF ANTIGENS RECOGNIZED ON HUMAN-MELANOMA CELLS BY A2-RESTRICTED CYTOLYTIC T-LYMPHOCYTES (CTL)

We have pursued our analysis of potential tumor-rejection antigens rec ognized on human melanoma by autologous cytolytic T lymphocytes (CTL). We reported previously that 3 distinct antigens (A,B,C) were recogniz ed on melanoma cell line SK29-MEL in association with HLA-A2. Selectio n for melanoma-cell variants resistant to anti-A CTL revealed that ant igen A consists of at least 2 determinants (Aa, Ab) which can be lost separately. Genetic linkage between Aa and Ab was suggested by concomi tant loss of Aa and Ab in an immunoselected tumor-cell variant. This v ariant was also resistant to an autologous CTL clone restricted by HLA -B45, indicating that this CTL may also recognize a determinant of ant igen A. Of 11 allogeneic HLA-A2 melanoma cell lines that were tested, 5 expressed both Aa and Ab, I expressed only Aa, and 1 only Ab. None o f them was lysed by anti-B or anti-C CTL clones. A CTL clone derived f rom another HLA-A2-melanoma patient was found to have exactly the same lytic pattern as the anti-Ab CTL of the first patient. This suggested that it may be possible to elicit an anti-Ab response in many HLA-A2 patients. We conclude that there are at least 2 distinct antigens pres ented in association with HLA-A2 that are common to many melanomas and therefore constitute promising targets for specific immunotherapy. (C ) 1993 Wiley-Liss, Inc.