Gress R E, Hodes R J
J Immunol. 1984 May;132(5):2226-31.
The influence of T cell genotype and T cell maturation environment on the generation of the T cell alloreactive repertoire was evaluated in the H-2b cytotoxic T lymphocyte response to Kb mutant determinants expressed by the strain B6-H-2bm6. Specifically, by constructing radiation bone marrow chimeras with B6 or B10 (H-2b) donor cells and B10.BR, B10.A(4R), B10.MBR, and B6.C-H-2bm1 irradiated mice as recipients, it was possible to investigate the major histocompatibility complex (MHC)-encoded gene products of the host environment required for the generation of a bm6-specific H-2b CTL response. The results of such experiments confirmed the previous finding that the alloreactive T cell repertoire is influenced both by T cell MHC genotype and by the MHC gene products of the T cell maturation environment. In addition, the results of the present study further demonstrated that in the chimeric donor and host genetic combinations used, it was both necessary and sufficient that there be a homology of K region-encoded determinants for the generation of a bm6-specific CTL response. Experiments utilizing a mixed responder population of unresponsive B6----B10.D2 spleen cells and responsive Lyt-2 congenic B6.Lyt-2.1 spleen cell suggested that the cellular defect(s) underlying the unresponsiveness of the chimeric cells to bm6-encoded determinants was at the level of the CTL precursor. Together, these findings indicate that an interaction of the K region-encoded gene products of the T cell and its maturation environment play a critical role in the generation of the CTL repertoire specific for bm6 mutant determinants. We discuss here the possibility that this interaction may reflect a requirement that T cells recognize such mutant allodeterminants in association with self restriction elements present on the same mutant K region-encoded molecule.
在对由B6 - H - 2bm6菌株表达的Kb突变决定簇的H - 2b细胞毒性T淋巴细胞反应中，评估了T细胞基因型和T细胞成熟环境对T细胞同种异体反应性库产生的影响。具体而言，通过用B6或B10（H - 2b）供体细胞与B10.BR、B10.A(4R)、B10.MBR和经辐照的B6.C - H - 2bm1小鼠作为受体构建辐射骨髓嵌合体，有可能研究产生bm6特异性H - 2b CTL反应所需的宿主环境的主要组织相容性复合体（MHC）编码的基因产物。此类实验结果证实了先前的发现，即同种异体反应性T细胞库受T细胞MHC基因型和T细胞成熟环境的MHC基因产物影响。此外，本研究结果进一步证明，在所使用的嵌合供体和宿主基因组合中，对于产生bm6特异性CTL反应而言，K区域编码的决定簇存在同源性既是必要的也是充分的。利用无反应性的B6→B10.D2脾细胞和有反应性的Lyt - 2同基因B6.Lyt - 2.1脾细胞的混合反应群体进行的实验表明，嵌合细胞对bm6编码决定簇无反应性的潜在细胞缺陷在于CTL前体细胞水平。这些发现共同表明，T细胞及其成熟环境的K区域编码基因产物之间的相互作用在产生针对bm6突变决定簇的CTL库中起关键作用。我们在此讨论这种相互作用可能反映T细胞识别此类突变异体决定簇与存在于同一突变K区域编码分子上的自身限制元件相关联这一需求的可能性。
