Functional anatomy of T cell activation and synapse formation.
T cell activation and function require a structured engagement of antigen-presenting cells. These cell contacts are characterized by two distinct dynamics in vivo: transient contacts resulting from promigratory junctions called immunological kinapses or prolonged contacts from stable junctions called immunological synapses. Kinapses operate in the steady state to allow referencing to self-peptide-MHC (pMHC) and searching for pathogen-derived pMHC. Synapses are induced by T cell receptor (TCR) interactions with agonist pMHC under specific conditions and correlate with robust immune responses that generate effector and memory T cells. High-resolution imaging has revealed that the synapse is highly coordinated, integrating cell adhesion, TCR recognition of pMHC complexes, and an array of activating and inhibitory ligands to promote or prevent T cell signaling. In this review, we examine the molecular components, geometry, and timing underlying kinapses and synapses. We integrate recent molecular and physiological data to provide a synthesis and suggest ways forward.
Fooksman
David R
DR
Department of Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, NYU School of Medicine, New York, 10016, USA. David.Fooksman@med.nyu.edu
Vardhana
Santosh
S
Vasiliver-Shamis
Gaia
G
Liese
Jan
J
Blair
David A
DA
Waite
Janelle
J
Sacristán
Catarina
C
Victora
Gabriel D
GD
Zanin-Zhorov
Alexandra
A
Dustin
Michael L
ML
D000818:Animals; D002450:Cell Communication; D006801:Humans; D054992:Immunological Synapses / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D011948:Receptors, Antigen, T-Cell