Institute for Biology III, Faculty of Biology, University of Freiburg, Freiburg, Germany; Centre for Biological Signalling Studies BIOSS, University of Freiburg, Freiburg, Germany.
Institute for Biology III, Faculty of Biology, University of Freiburg, Freiburg, Germany; Centre for Biological Signalling Studies BIOSS, University of Freiburg, Freiburg, Germany; Center for Chronic Immunodeficiency (CCI), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Adv Immunol. 2018;137:83-133. doi: 10.1016/bs.ai.2017.12.002. Epub 2018 Feb 13.
T and B lymphocytes are key players of the adaptive immune system. They recognize pathogenic cues via the T cell antigen receptor (TCR) and the B cell antigen receptor (BCR) to get activated and execute their protective function. TCR and BCR signaling are initiated at the plasma membrane and subsequently propagated into the cell, ultimately leading to cell activation and a protective immune response. However, inappropriate activation of T and B cells can be detrimental to the host resulting in autoimmune disorders, immunodeficiencies, and cancer. The TCR and BCR are located at the plasma membrane, which composition is highly heterogenic. Membrane compartmentalization based on specific lipid-lipid and protein-lipid interactions has raised the interest of the scientific community, converting the plasma membrane into an active player in the initiation of signaling and adding an additional layer of regulation to our current understanding of the functioning of antigen receptors. Caveolin-1 is an integral membrane protein and a crucial component of caveolae. It has been long thought that lymphocytes lack Caveolin-1 expression, due to the absence of detectable caveolae in lymphocytes and the failure to detect Caveolin-1 in T and B cell lines. However, Caveolin-1 is expressed at low levels in primary lymphocytes, and recent studies have shown the importance of Caveolin-1 for the basal membrane organization of the BCR and the TCR as well as their reorganization upon activation. Here, we review our current understanding of the initial signaling events of TCR and BCR activation with respect to receptor compartmentalization on the plasma membrane and with special emphasis on the previously unnoticed role of Caveolin-1.
T 和 B 淋巴细胞是适应性免疫系统的关键参与者。它们通过 T 细胞抗原受体 (TCR) 和 B 细胞抗原受体 (BCR) 识别病原体线索，从而被激活并执行其保护功能。TCR 和 BCR 信号在质膜起始，随后在细胞内传播，最终导致细胞激活和保护性免疫反应。然而，T 和 B 细胞的异常激活可能对宿主有害，导致自身免疫性疾病、免疫缺陷和癌症。TCR 和 BCR 位于质膜上，其组成高度异质。基于特定脂质-脂质和蛋白-脂质相互作用的膜区室化引起了科学界的兴趣，将质膜转化为信号起始的活跃参与者，并为我们目前对抗原受体功能的理解增加了额外的调节层。窖蛋白-1 是一种完整的膜蛋白，是小窝的关键组成部分。长期以来，人们认为淋巴细胞缺乏窖蛋白-1 的表达，因为在淋巴细胞中检测不到可检测的小窝，并且在 T 和 B 细胞系中也检测不到窖蛋白-1。然而，窖蛋白-1 在原代淋巴细胞中低表达，最近的研究表明窖蛋白-1 对 BCR 和 TCR 的基底膜组织以及它们在激活时的重排很重要。在这里，我们回顾了我们目前对 TCR 和 BCR 激活的初始信号事件的理解，特别是关于质膜上受体区室化的理解，并特别强调了窖蛋白-1以前未被注意到的作用。
