A SINGLE MONOCLONAL ANTI-la ANTIBODY INHIBITS ANTIGEN-SPECIFIC T CELL SUBREGIONS' PROLIFERATION CONTROLLED BY DISTINCT h GENES MAPPING IN DIFFERENT H-2 I

A xenogeneic rat anti-mouse la monoclonal antibody, M5/114 ( y P b , ~ ) , was studied for its effects in vitro on T cell proliferative responses. Strain distribution studies revealed that M5/114 could inhibit I-A subregion-restricted T cell responses of the H-2btd.qtU but not the H2'-**" haplotypes, indicating that this xenoantibody recognizes a polymorphic determinant on mouse la molecules. This same monoclonal antibody was found to inhibit BALB/c (H-2d) T cell proliferation to both GmA-" and G58L38@4. The Ir genes regulating responses to these antigens map to either the I-A subregion (GAT), or the I-A and I-E subregions (GL+), raising the possibility that M5/ 114 recognizes both I-A and I-E subregion-encoded la glycoproteins. It could be shown, using appropriate F1 responding cells, that M5/114 does in fact affect GAT and GL@ responses by interaction with both the I-A and the I-E subregion products, and not by any nonspecific effect resulting from binding to the I-A subregion product alone. These results are consistent with genetic and biochemical studies directly demonstrating that M5/114 recognizes A,Ap and E,E0 molecular complexes. The existence of a shared epitope on I-A and I-E subregion products suggests the possibility that these molecules arose by gene duplication. Finally, the precise correlation between the la molecules recognized by M5/114 and the ability of this antibody to block T cell responses under It gene control strengthens the hypothesis that la antigens are Ir gene products.