Hino T, Ishikawa H, Saito K
Department of Microbiology, Keio University School of Medicine, Tokyo, Japan.
J Immunol. 1988 Jan 1;140(1):44-51.
Previous study demonstrated that anti-H-43a cytotoxic T lymphocyte (CTL) response of H-43b CWB (H-2b) stain carrying non-major histocompatability complex (MHC) genes of C3H and F1 strains raised by crossing CWB with various H-43b strains was restricted exclusively by self H-2Kb (Kb). In the present study, newly produced C3W strain (H-2k, H-43b), which is H-43-congenic to C3H/HeN (H-2k, H-43a), was used as H-43b mice, and possibility of immunodominance of Kb was examined. No anti-H-43a CTL response could be induced in C3W strain and F1 strains raised by crossing C3W with other H-43b strains not carrying Kb. Thus, the possibility of immunodominance of Kb over the other MHC class I alleles could not be supported. We also examined possibility of epistatic effect of I region genes and non-MHC genes on the Kb restriction. (C3W x C57BL/6)F1(I-Ak/b) and (C3W x B6.CH-2bm12)F1(I-Ak/bm12)mice showed equally anti-H-43a CTL response restricted exclusively by self Kb, and (C3W x B10.MBR)F1(Ik/k) mice also showed anti-H-43a CTL response restricted solely by self Kb. Cold target competition experiments demonstrated that H-43b C57BL/10 or A.BY mice, which do not have non-MHC genes of C3H mounted anti-H-43a CTL response restricted solely by self Kb. Thus, no relation of I region genes or non-MHC genes to the Kb restriction was shown. All the results indicate that H-43b mouse strains, including F1, can not achieve anti-H-43a CTL response unless they carry Kb allele. Notably, (C3W x C57BL/6)F1 mice mounted self Kb-restricted anti-H-43a CTL response, whereas (C3W x B6.CH-2bm1)F1 mice carrying mutated Kb could not mount anti-H-43a CTL response at all. These findings indicate strongly that Kb itself is classical Ir gene of anti-H-43a CTL response and directs self Kb restriction of the response.
先前的研究表明，通过将CWB与各种H-43b品系杂交培育出的携带C3H和F1品系非主要组织相容性复合体（MHC）基因的H-43b CWB（H-2b）品系的抗H-43a细胞毒性T淋巴细胞（CTL）反应仅受自身H-2Kb（Kb）限制。在本研究中，新培育的C3W品系（H-2k，H-43b），它与C3H/HeN（H-2k，H-43a）是H-43同源的，被用作H-43b小鼠，并检测了Kb免疫显性的可能性。在C3W品系以及通过将C3W与其他不携带Kb的H-43b品系杂交培育出的F1品系中，均无法诱导出抗H-43a CTL反应。因此，无法支持Kb相对于其他MHC I类等位基因的免疫显性可能性。我们还检测了I区基因和非MHC基因对Kb限制的上位效应的可能性。（C3W×C57BL/6）F1（I-Ak/b）和（C3W×B6.CH-2bm12）F1（I-Ak/bm12）小鼠表现出同样仅受自身Kb限制的抗H-43a CTL反应，并且（C3W×B10.MBR）F1（Ik/k）小鼠也表现出仅受自身Kb限制的抗H-43a CTL反应。冷靶竞争实验表明，不具有C3H非MHC基因的H-43b C57BL/10或A.BY小鼠表现出仅受自身Kb限制的抗H-43a CTL反应。因此，未显示I区基因或非MHC基因与Kb限制有任何关系。所有结果表明，包括F1在内的H-43b小鼠品系，除非携带Kb等位基因，否则无法产生抗H-43a CTL反应。值得注意的是，（C3W×C57BL/6）F1小鼠产生了自身Kb限制的抗H-43a CTL反应，而携带突变Kb的（C3W×B6.CH-2bm1）F1小鼠根本无法产生抗H-43a CTL反应。这些发现有力地表明，Kb本身是抗H-43a CTL反应的经典Ir基因，并指导该反应的自身Kb限制。
