The molecular requirements for early activation of T cells are still being determined. In Nature, James & Vale report a reductionist approach to recapitulate the proximal events of TCR triggering. They selectively reconstitute HEK cells, which otherwise entirely lack T cell signaling molecules, with individual modules of T cell proximal activation. Using this approach they identify a minimal TCR activation unit that requires the kinases Lck and Zap70. Using antigen presenting cells they also interrogate the role of adhesion molecule and peptide major histocompatibility (pMHC) interactions. They observe classic TCR-pMHC immunological synapses with exclusion of T cell molecules like CD45. Stabilization of this structure and activation does not depend on productive signaling but solely on cognate TCR-pMHC interaction. Conversely, intracellular activation can occur even without pMHC or TCR but also with an equivalent but entirely artificial receptor-ligand system as long as CD45 is excluded from the immune synapse.

Nature 487, 64–69 (2012)