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Inhibition of T cell activation and function by the adaptor protein CIN85

Mei Suen Kong1,2, Akiko Hashimoto-Tane1, Yusuke Kawashima3,4

  • 1Laboratory for Cell Signaling, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.

Science Signaling
|February 7, 2019
PubMed

Insights

CIN85 adaptor protein limits T cell activation by associating with Sts-2. Lacking CIN85 enhances T cell responses like IL-2 production and proliferation following T cell receptor stimulation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • T cell activation relies on signaling molecules downstream of the T cell receptor (TCR), organized by adaptor proteins.
  • CIN85 (Cbl-interacting protein of 85 kDa) is an adaptor protein implicated in T cell signaling pathways.

Purpose of the Study:

  • To investigate the role of CIN85 in T cell activation and its mechanism of action.
  • To determine how CIN85 influences T cell responses to T cell receptor (TCR) stimulation.

Main Methods:

  • Comparative analysis of wild-type (WT) and CIN85-deficient T cells.
  • Assessment of T cell proliferation and IL-2 production.
  • Examination of CIN85 recruitment to the TCR signaling complex upon antigen stimulation.
  • Analysis of early TCR signaling events, including protein phosphorylation (Zap70, SLP76, Erk).
  • Investigation of CIN85's interaction with Sts-2 via its SH3 and PR regions.

Main Results:

  • T cells lacking CIN85 exhibited enhanced IL-2 production and proliferation compared to WT T cells after TCR stimulation.
  • CIN85 was recruited to the TCR signaling complex following stimulation of WT T cells.
  • Key early TCR signaling events, including Zap70, SLP76, and Erk phosphorylation, were amplified in CIN85-deficient T cells.
  • The inhibitory function of CIN85 was dependent on its SH3 and PR regions and its association with Sts-2.

Conclusions:

  • CIN85 acts as a negative regulator of T cell activation.
  • CIN85 is recruited to the TCR signaling complex and inhibits T cell activation through its interaction with Sts-2.
  • These findings elucidate a novel mechanism for controlling T cell responses mediated by the CIN85-Sts-2 complex.

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