Divergent changes in the sensitivity of maturing T cells to structurally related ligands underlies formation of a useful T cell repertoire
Divergent changes in the sensitivity of maturing T cells to structurally related ligands underlies formation of a useful T cell repertoire
复制标题
DOI：
10.1016/s1074-7613(00)80036-9
复制
发表时间：
1999-03-01
期刊：
影响因子：
32.4
通讯作者：
Germain, RN
中科院分区：
文献类型：
--
作者：
Lucas, B;Stefanová, I;Germain, RN
CD4(+)CD8(+)胸腺细胞分化需要自肽/MHC配体诱导的TCR信号传导。然而，由此产生的成熟 T 细胞不会被这些自身复合物激活，而外来配体可能是有效的刺激物。在这里，我们表明 TCR 的信号传导特性在胸腺细胞成熟过程中发生变化，对相关肽/MHC 分子复合物的反应产生不同的影响，并导致这种区别。 CD4(+)CD8(+)胸腺细胞的弱激动剂在发育过程中失去效力，伴随着TCR相关磷酸化从激动剂转变为部分激动剂/拮抗剂模式。相反，对强激动剂的敏感性得以保持，并且信号传导完整。这产生了对外来抗原高度敏感的成熟T细胞库，同时具有针对自身配体激活的广泛安全范围。
CD4(+)CD8(+) thymocyte differentiation requires TCR signaling induced by self-peptide/MHC ligands. Nevertheless, the resulting mature T cells are not activated by these self-complexes, whereas foreign ligands can be potent stimuli. Here, we show that the signaling properties of TCR change during thymocyte maturation, differentially affecting responses to related peptide/MHC molecule complexes and contributing to this discrimination. Weak agonists for CD4(+)CD8(+) thymocytes lose potency during development, accompanied by a change in TCR-associated phosphorylation from an agonist to a partial agonist/antagonist pattern. in contrast, sensitivity to strong agonists is maintained, along with full signaling. This yields a mature T cell pool highly responsive to foreign antigen while possessing a wide margin of safety against activation by self-ligands.