Sant'Angelo D B, Waterbury P G, Cohen B E, Martin W D, Van Kaer L, Hayday A C, Janeway C A
Section of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Immunity. 1997 Oct;7(4):517-24. doi: 10.1016/s1074-7613(00)80373-8.
The analysis of T cell receptor alpha (TCR alpha) chains in mice transgenic for a TCR beta chain has allowed us to demonstrate a central role for self-peptides in the positive intrathymic selection of major histocompatibility complex (MHC) class II-restricted T cells. Analysis of specific V alpha-J alpha joins in mature CD4+ TCRhigh thymocytes and in peripheral CD4+ T cells revealed a limitation in amino-acid sequences. By analysis of immature thymocytes, we could show that this limited repertoire was selected from a more diverse repertoire. By analysis of the same beta chain-transgenic mice bred to H-2Ma-deficient mice that express one or a very limited number of peptides, we could demonstrate that the V alpha-J alpha join repertoire was now altered and much more limited. Together, these data provide molecular and genetic evidence that the intrathymic positive selection of the TCR repertoire is critically affected by self-peptides presented by MHC class II molecules, most likely on thymic cortical epithelial cells.
对转染了TCRβ链的小鼠的T细胞受体α（TCRα）链进行分析，使我们能够证明自身肽在主要组织相容性复合体（MHC）II类限制性T细胞的胸腺内阳性选择中起核心作用。对成熟CD4+ TCR高表达胸腺细胞和外周CD4+ T细胞中特定Vα-Jα连接的分析揭示了氨基酸序列的局限性。通过对未成熟胸腺细胞的分析，我们可以表明这种有限的库是从更多样化的库中选择出来的。通过对与表达一种或非常有限数量肽的H-2Ma缺陷小鼠杂交的同一β链转基因小鼠的分析，我们可以证明Vα-Jα连接库现在发生了改变且更加有限。总之，这些数据提供了分子和遗传学证据，表明TCR库的胸腺内阳性选择受到MHC II类分子呈递的自身肽的严重影响，最有可能是在胸腺皮质上皮细胞上。
