Density of GM3 with normal primary structure determines mouse melanoma antigenicity; a new concept of tumor antigen

We attempted to induce anti-melanoma cytotoxic T cells (CTL) and suppressor T cells (Ts) inhibiting CTL generation by using liposomes carrying various densities of GM3 as tumor antigens. We found that liposomes carrying 6-16 mol% of GM3 with normal primary structure successfully generated anti-melanoma CTL and suppressor T cells, while liposomes with GM3 outside this range had little or no such activity. Anti-melanoma CTL induced by GM3(NeuGc)-liposomes belonged to CD4-/CD8- double-negative CD3+ CTL while GM3(NeuAc)-liposomes induced two types of T cells, CD4+ T cells and double-negative I-J positive T cells which mediated inhibition of the induction of anti-melanoma CTL responses. These cell types were the same as those induced by mitomycin C-treated melanoma cells for CTL induction and soluble melanoma antigen for Ts generation. The results clearly demonstrate that even GM3 with normal primary structure can, at a certain density, generate melanoma antigenicity.