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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A conformational change senses the strength of T cell receptor-ligand interaction during thymic selection
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A conformational change senses the strength of T cell receptor-ligand interaction during thymic selection

机译：在胸腺选择过程中，构象变化感应到T细胞受体-配体相互作用的强度

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摘要

T cell antigen receptor (TCR) triggering determines the fate of immature thymocytes. The affinity of the TCR for its endogenous peptide/MHC ligands serves as a signal for positive or negative selection through mechanisms that are still little understood. We have used a conformation-specific antibody to demonstrate that recognition of TCR ligands that lead to negative selection induces a conformational change in the TCR in situ. In contrast, this conformational change is elicited in only a small percentage of immature thymocytes during positive selection. Using a TUNEL assay, we demonstrate that the conformational change in the TCR is strongly linked to activation of programmed cell death in conditions leading to negative selection. Furthermore, the few conformational change-positive thymocytes detected in conditions that preferably lead to positive selection are also TUNEL-positive. Thus, the conformational change in the TCR may underlie the discrimination of ligands leading to positive and negative selection.
机译：T细胞抗原受体（TCR）的触发决定了未成熟胸腺细胞的命运。 TCR与其内源肽/ MHC配体的亲和力通过尚不十分清楚的机理作为阳性或阴性选择的信号。我们已经使用了构象特异性抗体来证明导致阴性选择的TCR配体的识别在原位诱导TCR的构象变化。相反，在阳性选择过程中，这种构象变化仅在少量的未成熟胸腺细胞中引起。使用TUNEL分析，我们证明TCR的构象变化与导致阴性选择的条件下程序性细胞死亡的激活密切相关。此外，在优选导致阳性选择的条件下检测到的少数构象变化阳性胸腺细胞也是TUNEL阳性的。因此，TCR中的构象变化可能是导致阳性和阴性选择的配体区别的基础。

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