Relation of cell surface antigens on methylcholanthrene-induced fibrosarcomas to immunoglobulin heavy chain complex variable region-linked T cell interaction molecules.

For optimal activation, T suppressor cells must receive a signal froma specialized inducer cell. The activating signal is delivered by a molecular complex that is composed, in part, of polymorphic gene products that are controlled by the immunoglobulin heavy chain complex (Igh) and that map to the variable region (Igh-V) of the complex. Consequently, if suppressor/inducer cells and their acceptor cells do not share Igh-V-encoded polymorphisms, the inducer molecules fail to activate the suppressor cells. Other polymorphic gene products (those that act as transplantation antigens on methylcholanthrene-induced fibrosarcomas) have been shown to be encoded by a gene(s) that maps to the same general region of chromosome 12 as does the Igh complex. Therefore, we tested the hypothesis that polymorphic gene products expressed by the T suppressor/inducer cell and its biologically active product were related to the transplantation antigens on these fibrosarcomas. We have found that isoantisera directed to a number of BALB/c methylcholanthrene-induced tumors block the induction of T suppressor cells but they do so only if the inducer or acceptor T cell (or both) expresses BALB/c Igh-linked polymorphisms. All other BALB/c gene products are irrelevant. These findings suggest that "transformation related antigens" on some sarcoma cells are variants of, or are otherwise related to, the cell interaction molecules that T cell subsets use to communicate with one another under normal circumstances. Furthermore, the findings that (a) multiple methylcholanthrene-induced tumors express serologically related antigens (as well as the unique ones that have been previously demonstrated by transplantation tests) and (b) these serologically related antigens can be found on Igh-V-controlled T cell communication molecules raise the intriguing possibility that, like certain viruses, methylcholanthrene reacts with specific regions of cellular DNA that either directly or indirectly regulate the expression of other specific genes (in this particular case the genes that encode the T cell communication molecules).