Distinct H-2-linked Ir genes control both antibody and T cell responses to different determinants on the same antigen, myoglobin.

The murine antibody and T lymphocyte proliferative responses to sperm whale myoglobin (Mb) were found to be under control of two distinct H-2-linked immune response (Ir) genes (Ir-Mb-1, mapping in the I-A subregion, and Ir-Mb-2, mapping in I-C). H-2(d) mice (B10.D2 and DBA/2), with both genes, were high responders to Mb and its fragments for both antibody secretion and T cell proliferation, while H-2(b) (B10) and H-2(k) (B10.BR) mice were low responders. Strains with only Ir-Mb-2 [B10.A and B10.A(5R)], which were intermediate responders to Mb, made antibodies to and proliferated in response to the NH(2)-terminal fragment (1-55) but not the COOH-terminal fragment (132-153) when immunized with Mb. In contrast, mice carrying only the Ir-Mb-1 gene (D2.GD and B10.GD) made antibodies to and proliferated in response to both fragments. However, their proliferation to fragment (1-55) was often lower than that of their congenic high responders (DBA/2 and B10.D2, respectively), possibly because they respond to only some of the determinants on this NH(2)-terminal fragment. Thus, these data demonstrate that distinct Ir genes, mapping in separate I-subregions of H-2, control responses to different antigenic determinants on the same protein molecule. Moreover, the gene that controls the T lymphocyte responses to a given determinant also controls production of antibodies specific for that same determinant (or a closely associated one).