The organization of the T-cell's plasma membrane continues to nourish the curiosity of immunologists, cell biologists and biophysicists. The main reason is the biological and biomedical interest to understand the workings of the cell–cell communication network activated by T-cells during an immune response. The molecular armamentarium of the T-cell plasma membrane helps to identify with high sensitivity, specificity and rapidity antigens from invading microbial pathogens and prepare adequate countermeasures to fend them off, while protecting from attacks against our normal tissues. Many T-cell membrane proteins act as receptors to carry out and finely tune these complex tasks. However, the TCR (T-cell receptor) holds a decisive hegemony for its crucial contribution in steering T-cell function and fate. An emerging notion is that TCR proximal signalling occurs at submicrometre-scale membrane domains. In the present chapter, we discuss the current knowledge on the TCR structure and the associated signal transduction machinery and how the notion of membrane nanodomains has decisively contributed to further understand the molecular basis of T-cell activation.

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