Choi E Y, Park W S, Jung K C, Chung D H, Bae Y M, Kim T J, Song H G, Kim S H, Ham D I, Hahn J H, Kim J, Kim K, Hwang T S, Park S H
Department of Pathology, Seoul National University College of Medicine, Korea.
Hum Immunol. 1997 Apr 15;54(1):15-20. doi: 10.1016/s0198-8859(97)00012-8.
We previously demonstrated the expression of MHC class II molecules in a significant percentage of human fetal and postnatal thymocytes. These results, at that time, raised the question as to whether the MHC class II molecules on immature thymocytes could actively be involved in the selection of immature T cells. We have developed a human reaggregate culture system to address this issue. Surprisingly, despite the fact that thymic epithelial cells (TECs) have been shown to be a major selecting cell type of positive selection, we were clearly able to see the involvement of MHC class II+ thymocytes during selection process through T-T interaction. In addition, maturation to single positive (SP) cells occurred only in the presence of MHC class II molecules and immature thymocytes were found to be arrested at the double positive (DP) stage of differentiation by blocking of TCR recognition of MHC class II molecules. All these results strongly suggest that human MHC class II+ thymocytes actively participate in the selection of the TCR repertoire, for which TCR recognition of peptide/MHC class II may be an initial determining step.
我们之前证明了在相当比例的人类胎儿期和出生后胸腺细胞中存在MHC II类分子的表达。当时,这些结果引发了一个问题,即未成熟胸腺细胞上的MHC II类分子是否能积极参与未成熟T细胞的选择。我们开发了一种人类重聚集培养系统来解决这个问题。令人惊讶的是,尽管胸腺上皮细胞(TECs)已被证明是阳性选择的主要选择细胞类型,但我们通过T-T相互作用清楚地看到了MHC II⁺胸腺细胞在选择过程中的参与。此外,只有在存在MHC II类分子的情况下才会成熟为单阳性(SP)细胞,并且发现未成熟胸腺细胞通过阻断TCR对MHC II类分子的识别而停滞在双阳性(DP)分化阶段。所有这些结果都强烈表明,人类MHC II⁺胸腺细胞积极参与TCR库的选择,对于此过程,TCR对肽/MHC II类分子的识别可能是一个初始决定步骤。