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Annu Rev Immunol. 2015;33:539-61. doi: 10.1146/annurev-immunol-032414-112158.

Early T cell activation: integrating biochemical, structural, and biophysical cues.

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Centre d'Immunologie de Marseille-Luminy and Centre d'Immunophénomique, Aix-Marseille Université, INSERM U1104 and US012, CNRS UMR7280 and UMS3367, 13288 Marseille Cedex 09, France; email:


T cells carry out the formidable task of identifying small numbers of foreign antigenic peptides rapidly and specifically against a very noisy environmental background of endogenous self-peptides. Early steps in T cell activation have thus fascinated biologists and are among the best-studied models of cell stimulation. This remarkable process, critical in adaptive immune responses, approaches and even seems to exceed the limitations set by the physical laws ruling molecular behavior. Despite the enormous amount of information concerning the nature of molecules involved in the T cell antigen receptor (TCR) signal transduction network, and the description of the nanoscale organization and real-time analysis of T cell responses, the general principles of information gathering and processing remain incompletely understood. Here we review currently accepted key data on TCR function, discuss the limitations of current research strategies, and suggest a novel model of TCR triggering and a few promising ways of going further into the integration of available data.


T cell antigen receptor; mechanosensing; mesoscale properties; self-awareness; signal processing; signal transduction

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