Selective loss of antigen-specific Ir gene function in IA mutant B6.C-H-2bm12 is an antigen presenting cell defect.
Immune responses to several soluble antigens were compared between B6.C-H-2bm12 mutant and wild-type B6 mice by using a lymph node T-cell proliferation assay. B6.C-H-2bm12 mice failed to respond to beef insulin whereas other IA gene-controlled responses, such as response to poly(L-Tyr, L-Glu)--poly(DL-Ala, L-Lys) and collagen, were indistinguishable between mutant and wild-type mice. The responses to multideterminant antigens such as ovalbumin and purified protein derivative of tuberculin were also found to be comparable in B6.C-H-2bm12 and B6 mice, thus indicating that this mutation resulted in a selective loss of the ability to respond to a certain antigen(s)--e.g., beef insulin. Populations depleted of adherent cells have been used to examine the mechanism by which Ia molecules mediate Ir gene control of antigen recognition. We show that the nonresponsiveness to beef insulin in the mutant mouse is the result of defective antigen presentation. In addition, we find that F1 hybrids between two nonresponders--B6.C-H-2bm12 and B10.A or B10.AKM (IAk) mice--become responders to beef insulin, thus demonstrating gene complementation. These findings taken together with other serologic and biochemical studies in the B6.C-H-2bm12 present convincing genetic evidence for the direct association of the A beta polypeptide chain of the Iab molecules with the expression of immune responsiveness to beef insulin. Study of the B6.C-H-2bm12 mouse should provide new insight into the cellular and molecular mechanisms by which Ir genes determine the nature of the immune response.
D000818:Animals; D006183:H-2 Antigens / Q000235:genetics*; D007111:Immunity, Cellular; D007328:Insulin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D006183:H-2 Antigens; D007328:Insulin