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 recognized on human melanoma by autologous cytolytic T lymphocytes (CTL). We reported previously that 3 distinct antigens (A,B,C) were recognized on melanoma cell line SK29-MEL in association with HLA-A2. Selection for melanoma-cell variants resistant to anti-A CTL revealed that antigen A consists of at least 2 determinants (Aa, Ab) which can be lost separately. Genetic linkage between Aa and Ab was suggested by concomitant loss of Aa and Ab in an immunoselected tumor-cell variant. This variant was also resistant to an autologous CTL clone restricted by HLA-B45, indicating that this CTL may also recognize a determinant of antigen A. Of 11 allogeneic HLA-A2 melanoma cell lines that were tested, 5 expressed both Aa and Ab, 1 expressed only Aa, and 1 only Ab. None of them was lysed by anti-B or anti-C CTL clones. A CTL clone derived from 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 presented in association with HLA-A2 that are common to many melanomas and therefore constitute promising targets for specific immunotherapy.
Wölfel
T
T
I. Medizinische Klinik und Poliklinik, Johannes Gutenberg-Universität, Mainz, Germany.
Hauer
M
M
Klehmann
E
E
Brichard
V
V
Ackermann
B
B
Knuth
A
A
Boon
T
T
Meyer Zum Büschenfelde
K H
KH
D000951:Antigens, Neoplasm / Q000032:analysis* / Q000235:genetics; D003001:Cloning, Molecular; D003601:Cytotoxicity Tests, Immunologic; D000939:Epitopes; D015789:HLA-A2 Antigen / Q000032:analysis* / Q000235:genetics; D015235:HLA-B Antigens / Q000032:analysis* / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D000939:Epitopes; D015789:HLA-A2 Antigen; D015235:HLA-B Antigens