title: Functional anatomy of T cell activation and synapse formation.
abstract: 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.
authors.affiliation: Department of Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, NYU School of Medicine, New York, 10016, USA. David.Fooksman@med.nyu.edu
authors.forename: David R
authors.initials: DR
authors.lastname: Fooksman
authors.forename: Santosh
authors.initials: S
authors.lastname: Vardhana
authors.forename: Gaia
authors.initials: G
authors.lastname: Vasiliver-Shamis
authors.forename: Jan
authors.initials: J
authors.lastname: Liese
authors.forename: David A
authors.initials: DA
authors.lastname: Blair
authors.forename: Janelle
authors.initials: J
authors.lastname: Waite
authors.forename: Catarina
authors.initials: C
authors.lastname: Sacristán
authors.forename: Gabriel D
authors.initials: GD
authors.lastname: Victora
authors.forename: Alexandra
authors.initials: A
authors.lastname: Zanin-Zhorov
authors.forename: Michael L
authors.initials: ML
authors.lastname: Dustin
mesh_terms: 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
chemical_list: D011948:Receptors, Antigen, T-Cell