TCR ITAM multiplicity is required for the generation of follicular helper T-cells

Nat Commun. 2015 May 11:6:6982. doi: 10.1038/ncomms7982.

Abstract

The T-cell antigen receptor (TCR) complex contains 10 copies of a di-tyrosine Immunoreceptor-Tyrosine-based-Activation-Motif (ITAM) that initiates TCR signalling by recruiting protein tyrosine kinases. ITAM multiplicity amplifies TCR signals, but the importance of this capability for T-cell responses remains undefined. Most TCR ITAMs (6 of 10) are contributed by the CD3ζ subunits. We generated 'knock-in' mice that express non-signalling CD3ζ chains in lieu of wild-type CD3ζ. Here we demonstrate that ITAM multiplicity is important for the development of innate-like T-cells and follicular helper T-cells, events that are known to require strong/sustained TCR-ligand interactions, but is not essential for 'general' T-cell responses including proliferation and cytokine production or for the generation of a diverse antigen-reactive TCR repertoire.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antigens / immunology
  • Cell Proliferation
  • Clone Cells
  • Female
  • Immunologic Memory
  • Immunoreceptor Tyrosine-Based Activation Motif*
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Natural Killer T-Cells / cytology
  • Natural Killer T-Cells / immunology
  • Receptors, Antigen, T-Cell / chemistry*
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, Antigen, T-Cell, alpha-beta / chemistry
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Receptors, Antigen, T-Cell, gamma-delta / chemistry
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • Signal Transduction
  • Structure-Activity Relationship
  • T-Lymphocytes, Helper-Inducer / cytology*

Substances

  • Antigens
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta