Self-recognition promotes the foreign antigen sensitivity of naive T lymphocytes
Self-recognition promotes the foreign antigen sensitivity of naive T lymphocytes
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DOI：
10.1038/nature01146
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发表时间：
2002-11-28
期刊：
影响因子：
64.8
通讯作者：
Germain, RN
中科院分区：
文献类型：
--
作者：
Stefanová, I;Dorfman, JR;Germain, RN
主要组织相容性复合物（MHC）I类和II类分子是高度多态性的蛋白质，其结合并呈递外源肽至T淋巴细胞的克隆分布的α受体（TCR）。作为一个群体，胸腺中产生的未成熟T淋巴细胞表达一组非常多样化的TCR特异性。阳性选择的过程过滤了这一广泛的库，以优化外周T细胞在可用MHC产物的背景下的抗原识别。只有那些其TCR对与表达的MHC蛋白结合的自身肽产生足够但不过度的信号反应的前体T细胞才能成功成熟（1）。在这里，我们表明，胸腺后的自我识别促进成熟T细胞的抗原反应性。T细胞与自身肽MHC配体接触的实验和生理中断导致信号传导和对外来刺激的反应敏感性迅速下降。由于适应性免疫系统必须在感染过程的早期招募，当抗原是有限的（2），这些发现表明，积极选择确保可预测的T细胞识别可用的自身配体，这反过来又促进了对病原体的有效反应。
Major histocompatibility complex (MHC) class I and II molecules are highly polymorphic proteins that bind and present foreign peptides to the clonally distributed alphabeta receptors (TCR) of T lymphocytes. As a population, the immature T lymphocytes generated in the thymus express a very diverse set of TCR specificities. A process of positive selection filters this broad repertoire to optimize peripheral T cells for antigen recognition in the context of available MHC products. Only those precursor T cells whose TCRs generate an adequate but not excessive signalling response to self-peptides bound to the expressed MHC proteins undergo successful maturation(1). Here we show that post-thymic self-recognition facilitates the antigen reactivity of mature T cells. Both experimental and physiological interruption of T-cell contact with self-peptide MHC ligands leads to a rapid decline in signalling and response sensitivity to foreign stimuli. Because the adaptive immune system must be recruited early in an infectious process when antigen is limiting(2), these findings suggest that positive selection ensures predictable T-cell recognition of available self-ligands, which in turn promotes efficient responses to pathogens.