Analysis of melanoma antigen and its involvement in tumor-escape mechanisms.
Melanoma antigen was characterized by using the C57BL/6 mouse melanoma (B16) system, especially in relation to escape mechanisms of tumor cells from immunological surveillance. The antigen on the surface of melanoma cells selectively induced double negative cytotoxic T lymphocytes (CTL) lacking genetic restriction specificity in their action, whereas the soluble antigen shed or secreted from the cells preferentially induced suppressor T cells (Ts) inhibiting CTL generation in the induction phase. The epitopes of melanoma antigen for CTL and Ts were found to possess a "GM3-like structure". Anti-melanoma CTL activity was blocked by either GM3(NeuAc)-or GM3(NeuGc)-liposomes. Moreover, the GM3 (NeuGc)-liposome could induce anti-melanoma CTL when used as an antigen in the in vitro primary response. On the other hand, the soluble melanoma antigen or GM3(NeuAc)-but not GM3(NeuGc)-liposome itself specifically induced anti-melanoma Ts. Therefore, anti-melanoma Ts are able to distinguish GM3 molecular species. We also found two types of T cells, C3T4+ and double negative I-J+ T cells, to be involved in this suppression. Although the primary structure of melanoma GM3 was demonstrated to be the same as that of normal GM3, syngeneic anti-melanoma GM3 monoclonal antibody (M2590) did distinguish melanoma from normal cells. Further close analysis in liposome lysis experiments using various concentrations of GM3 clearly demonstrated that M2590 anti-melanoma GM3 only reacted with GM3 at a "high" density (more than 10-12 mol%), whereas no reactivity was observed at a "low" density (less than 7.5 mol%). It is clear, therefore, that the density of GM3 with normal primary structure is important in generating melanoma antigenicity.(ABSTRACT TRUNCATED AT 250 WORDS)
Taniguchi
M
M
Division of Molecular Immunology, School of Medicine, Chiba University, Japan.
Sakatsume
M
M
Harada
Y
Y
Nores
G A
GA
Hakomori
S
S
D000818:Animals; D000951:Antigens, Neoplasm / Q000502:physiology*; D005679:G(M3) Ganglioside / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology*; D058950:Melanoma-Specific Antigens; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000951:Antigens, Neoplasm; D005679:G(M3) Ganglioside; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins