The nature of the immune response (Ir) gene defect for pigeon cytochrome c in [B10.A(4R) x B10.PL]F1 mice: A Comparison Between Thymic Selection and Antigen Presentation

[B10.A(4R) x B10.PL]F₁ mice are low responders to pigeon cytochromec, while [B10.A(2R) x B10.PL]F₁ and B10.A mice are high responders.The in vivo site at which the different aliomorphs of the E_aIa molecule exert their Ir gene effect on the immune responseto pigeon cytochrome c was examined by creating two differentsets of radiation-induced bone marrow chimeras. [B10.A(4R) xB10.PL]F₁(b.m.) B10.A(lrr.) chimeras, which possess antigen-presentingcells (APC) of the low responder, but whose T cells are educatedin a high responder environment, were found to be low respondersto pigeon cytochromec. In contrast, B10.A(b.m.) [B10.A(4R)x B10.PL]F₁(lrr.) chimeras, which possess APC of the high respondertype, but whose T cells are educated in a low responder environment,responded to pigeon cytochrome c Addition of B10.A APC to thefirst type of chimera, both prior to antigen priming and atthe time of the secondary challenge in vitro, converted 50%of the animals to responders Furthermore, [B10.A(4R) x B10.PL]F₁mice responded to pigeon cytochrome c If they were primed witha 10-fold greater antigen dose and restimulated in vitro Inthe presence of B10.A APC. These results suggest that the primarysite of the Ir gene defect in this system is at the level ofantigen presentation and not in the T cell repertoire.