Kovac Z, Schwartz R H
Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Int Immunol. 1989;1(1):1-10. doi: 10.1093/intimm/1.1.1.
[B10.A(4R) x B10.PL]F1 mice are low responders to pigeon cytochrome c, while [B10.A(2R) x B10.PL]F1 and B10.A mice are high responders. The in vivo site at which the different allomorphs of the E alpha Ia molecule exert their Ir gene effect on the immune response to pigeon cytochrome c was examined by creating two different sets of radiation-induced bone marrow chimeras. [B10.A(4R) x B10.PL]F1(b.m.)----B10.A(irr.) chimeras, which possess antigen-presenting cells (APC) of the low responder, but whose T cells are educated in a high responder environment, were found to be low responders to pigeon cytochrome c. In contrast, B10.A(b.m.)----[B10.A(4R) x B10.PL]F1(irr.) chimeras, which possess APC of the high responder type, but whose T cells are educated in a low responder environment, responded to pigeon cytochrome c. Addition of B10.A APC to the first type of chimera, both prior to antigen priming and at the time of the secondary challenge in vitro, converted 50% of the animals to responders. Furthermore, [B10.A(4R) x B10.PL]F1 mice responded to pigeon cytochrome c if they were primed with a 10-fold greater antigen dose and restimulated in vitro in the presence of B10.A APC. These results suggest that the primary site of the Ir gene defect in this system is at the level of antigen presentation and not in the T cell repertoire.
[B10.A(4R)×B10.PL]F1小鼠对鸽细胞色素c反应较弱，而[B10.A(2R)×B10.PL]F1小鼠和B10.A小鼠则反应较强。通过构建两组不同的辐射诱导骨髓嵌合体，研究了Eα Ia分子的不同同种异型在体内对鸽细胞色素c免疫反应发挥Ir基因效应的位点。发现[B10.A(4R)×B10.PL]F1（骨髓）----B10.A（辐照）嵌合体对鸽细胞色素c反应较弱，该嵌合体具有反应较弱小鼠的抗原呈递细胞（APC），但其T细胞是在反应较强的环境中发育的。相反，B10.A（骨髓）----[B10.A(4R)×B10.PL]F1（辐照）嵌合体对鸽细胞色素c有反应，该嵌合体具有反应较强类型的APC，但其T细胞是在反应较弱的环境中发育的。在抗原致敏前以及体外再次攻击时，向第一类嵌合体中添加B10.A APC，可使50%的动物转变为反应者。此外，如果用高10倍的抗原剂量对[B10.A(4R)×B10.PL]F1小鼠进行致敏，并在B10.A APC存在的情况下进行体外再刺激，它们对鸽细胞色素c有反应。这些结果表明，该系统中Ir基因缺陷的主要位点在抗原呈递水平，而非T细胞库。
