Table 1.

Recent models for initial TCR triggering

Model	Description
Piston-like movement	An external force from the APC/T cell interaction pushes the TCR/CD3 complex in a piston-like fashion perpendicular to the plasma membrane, exposing activating motifs on the intracellular regions of CD3 chains
Receptor-deformation	The force of the motility of the T cell as it moves over an APC induces TCR triggering only when pMHC/TCR interactions are of a high enough affinity to withstand the force long enough to undergo a conformational change
Permissive geometry	pMHC dimers bind TCR/CD3 dimers inducing a rotational scissor-like conformational change in CD3 chain(s) that reveal previously hidden intracellular activation motif(s)
Kinetic segregation	Signal initiation occurs due to exclusion of inhibitory molecules in the tight contact zone between the T cell and the APC, thereby shifting the enzymatic steady state towards an activating state
Diffusion trapping	Expanded kinetic segregation model in which the affinity/diffusion coefficient of the pMHC/TCR dictates the valency of TCRs required to “trap” the complex in the tight contact zone and therefore initiate a productive signal
Pseudodimer	Agonist pMHC/TCR recruits a second TCR via interaction with its associated CD4, the second TCR then binds a “co- agonist” endogenous pMHC forming a stable pseudodimer that triggers signaling via proximity of ITAMs to CD4- associated lck and/or by conformational change