T cells stimulation by antigen (peptide-MHC, pMHC) initiates adaptive immunity, a major factor contributing to vertebrate fitness. The T cell antigen receptor (TCR) present on the surface of T cells is the critical sensor for the recognition of and response to “foreign" entities, including microbial pathogens and transformed cells. Much is known about the complex molecular machine physically connected to the TCR to initiate, propagate and regulate signals required for cellular activation. However, we largely ignore the physical distribution, dynamics and reaction energetics of this machine before and after TCR binding to pMHC. I will illustrate a few basic notions of TCR signalling and potent quantitative in-cell approaches used to interpret TCR signalling behaviour. I will provide two examples where mathematical formalisation will be welcome to better understand the TCR signalling process.
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