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Modulation of TCR responsiveness by the Grb2-family adaptor, Gads

Jennie Lugassy1, Jasmin Corso2, Dvora Beach1

  • 1Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel.

Cellular Signalling
|December 3, 2014
PubMed

Insights

Researchers developed Gads-deficient T cells using TALENs to study T cell receptor (TCR) signaling. Gads amplifies TCR signals, enhancing T cell responsiveness to weak stimuli and CD69 expression.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • T cell receptor (TCR) signaling involves SLP-76, Gads, and LAT adaptor proteins.
  • Gads acts as a crucial bridge in TCR-induced signaling pathways.
  • Previous research lacked specific tools to study Gads function.

Purpose of the Study:

  • To generate Gads-deficient T cells for studying its role in TCR signaling.
  • To investigate Gads' function in T cell activation and sensitivity.
  • To explore Gads phosphorylation and its impact on TCR responsiveness.

Main Methods:

  • TALEN-directed genome editing was used to create Gads-deficient Jurkat T cells.
  • Mass spectrometry was employed to identify Gads phosphorylation sites.
  • TCR-induced signaling events like CD69 expression and calcium flux were analyzed.

Main Results:

  • Gads is essential for amplifying TCR-induced CD69 expression.
  • Gads confers responsiveness to weak TCR stimuli, promoting PLC-γ1 phosphorylation and calcium flux.
  • Phosphorylation of Gads at T262 enhances TCR responsiveness and sensitivity to weak stimuli.

Conclusions:

  • TALEN-based reverse genetics is feasible in Jurkat T cells for studying adaptor proteins.
  • Gads is a critical regulator of TCR signaling sensitivity.
  • Gads acts as a dose-dependent amplifier, modulating T cell responses to varying TCR stimulation strengths.
Keywords:
Adaptor proteinGadsT cell receptor (TCR)Transcription activator-like effector nuclease (TALEN)

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