TCR Signal Strength Influences alphabeta/gammadelta Lineage Fate

Immunity. 2005 May;22(5):583-93. doi: 10.1016/j.immuni.2005.03.014.

Abstract

Signals transduced by T cell antigen receptors (TCRs) have been shown to be critical for alphabeta and gammadelta T cell development, but their role in lineage determination remains poorly defined. Two models have been forwarded for alphabeta/gammadelta lineage choice: the instructive model and the stochastic model. Recent data, however, are inconsistent with either model. In this study, we devised an experimental system in which lineage fate was controlled exclusively by the gammadeltaTCR. We then analyzed the impact of TCR signal strength on alphabeta/gammadelta lineage development by altering the surface expression or signaling potential of the gammadeltaTCR complex. We found that increasing the gammadeltaTCR signal strength favored gammadelta lineage development, whereas weakening the gammadeltaTCR signal favored alphabeta lineage development. These results support a model in which the strength of the TCR signal is a critical determinant in the lineage fate decision.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Differentiation / immunology
  • DNA, Complementary / genetics
  • Humans
  • In Vitro Techniques
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Immunological
  • Receptors, Antigen, T-Cell, alpha-beta / deficiency
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism*
  • Receptors, Antigen, T-Cell, gamma-delta / deficiency
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Signal Transduction
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology*

Substances

  • DNA, Complementary
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • Recombinant Proteins