Functional anatomy of T cell activation and synapse formation

David R. Fooksman, Santosh Vardhana, Gaia Vasiliver-Shamis, Jan Liese, David A. Blair, Janelle Waite, Catarina Sacristán, Gabriel D. Victora, Alexandra Zanin-Zhorov, Michael L. Dustin

Research output: Contribution to journalReview articlepeer-review

285 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)79-105
Number of pages27
JournalAnnual Review of Immunology
Volume28
DOIs
StatePublished - Apr 23 2010
Externally publishedYes

Keywords

  • Immunological synapse
  • Kinapse
  • Microcluster
  • TCR triggering

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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