Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, Australia.
Int J Mol Sci. 2020 Dec 23;22(1):68. doi: 10.3390/ijms22010068.
T cells are a critical part of the adaptive immune system that are able to distinguish between healthy and unhealthy cells. Upon recognition of protein fragments (peptides), activated T cells will contribute to the immune response and help clear infection. The major histocompatibility complex (MHC) molecules, or human leukocyte antigens (HLA) in humans, bind these peptides to present them to T cells that recognise them with their surface T cell receptors (TCR). This recognition event is the first step that leads to T cell activation, and in turn can dictate disease outcomes. The visualisation of TCR interaction with pMHC using structural biology has been crucial in understanding this key event, unravelling the parameters that drive this interaction and their impact on the immune response. The last five years has been the most productive within the field, wherein half of current unique TCR-pMHC-I structures to date were determined within this time. Here, we review the new insights learned from these recent TCR-pMHC-I structures and their impact on T cell activation.
T 细胞是适应性免疫系统的重要组成部分，能够区分健康细胞和不健康细胞。在识别蛋白质片段（肽）后，活化的 T 细胞将有助于免疫反应并帮助清除感染。主要组织相容性复合体（MHC）分子，或人类白细胞抗原（HLA）在人类中，将这些肽结合到呈现给 T 细胞的 MHC 分子上，T 细胞用其表面的 T 细胞受体（TCR）识别它们。这种识别事件是导致 T 细胞活化的第一步，反过来又可以决定疾病的结局。使用结构生物学可视化 TCR 与 pMHC 的相互作用对于理解这一关键事件至关重要，揭示了驱动这种相互作用的参数及其对免疫反应的影响。过去五年是该领域最具成效的时期，在此期间，目前为止已确定的一半独特的 TCR-pMHC-I 结构都是在这段时间内确定的。在这里，我们回顾了从这些最近的 TCR-pMHC-I 结构中获得的新见解及其对 T 细胞活化的影响。
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