Similarities between transplantation antigens on methylcholanthrene-induced sarcomas and T-cell regulatory molecules.
Successful interaction among T-cell subsets requires, among other things, homology at certain genetic loci that code for cellular interaction molecules (CIM). One such interaction, the induction of an acceptor-cell population by an Ly-1 T-suppressor-inducer cell, is controlled by genes that map to the variable region of the immunoglobulin heavy chain (Igh) complex. If the suppressor-induced cells (or their cell-free products) do not share Igh-V polymorphisms with their acceptor cells, the induction event fails to take place. Recently, structural genes of a transplantation antigen on the methylcholanthrene-induced sarcoma Meth A were mapped to the same region of chromosome 12 as the Igh gene complex. We tested whether there was any relationship between the Meth A transplantation antigen and T-cell regulatory molecules by using antisera against the Meth A antigen to block this particular Igh-linked T-T interaction. We found that isoantisera against a large number of methylcholanthrene-induced sarcomas tested were capable of blocking the induction of T-suppressor cells so long as the inducer and acceptor cells bore the Igha polymorphism. Further, we found a structural gene on MC-induced tumors that could absorb out this activity, and the structural gene for this antigen is coded for the same region as the Igh gene loci. The antisera binds to the I-J+ portion of a T-cell regulatory molecule Ly-1 TsiF, the portion of the molecule that has no specificity for antigen and imparts the Igh-linked genetic restriction. The implications of these findings for both oncology and immunology were discussed.
D000818:Animals; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000276:immunology; D005796:Genes; D006649:Histocompatibility Antigens / Q000235:genetics / Q000276:immunology*; D007106:Immune Sera / Q000276:immunology; D007108:Immune Tolerance; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000951:Antigens, Neoplasm; D006649:Histocompatibility Antigens; D007106:Immune Sera; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D008748:Methylcholanthrene