Rap1A positively regulates T cells via integrin activation rather than inhibiting lymphocyte signaling

Nat Immunol. 2002 Mar;3(3):251-8. doi: 10.1038/ni765. Epub 2002 Feb 11.

Abstract

T cell receptor (TCR) stimulation activates the small GTPase Rap1A, which is reported to antagonize Ras signaling and induces T cell anergy. To address its role in vivo, we generated transgenic mice that constitutively expressed active Rap1A within the T cell lineage. We found that active Rap1A did not interfere with the Ras signaling pathway or antagonize T cell activation. Instead of anergy, the T lymphocytes that constitutively expressed active Rap1A showed enhanced TCR-mediated responses, both in thymocytes and mature T cells. In addition, Rap1A activation was sufficient to induce strong activation of the beta1 and beta2 integrins via an avidity-modulation mechanism. This shows that, far from playing an inhibitory role during T cell activation, Rap1A positively influences T cells by augmenting lymphocyte responses and directing integrin activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD18 Antigens / physiology*
  • Enzyme Activation
  • Humans
  • Immune Tolerance
  • Integrin beta1 / physiology*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lymphocyte Activation
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Mice
  • Mice, Transgenic
  • Mitogen-Activated Protein Kinases / metabolism
  • Receptors, Antigen, T-Cell / physiology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / physiology
  • rap1 GTP-Binding Proteins / physiology*

Substances

  • CD18 Antigens
  • Integrin beta1
  • Lymphocyte Function-Associated Antigen-1
  • Receptors, Antigen, T-Cell
  • Intercellular Adhesion Molecule-1
  • Mitogen-Activated Protein Kinases
  • rap1 GTP-Binding Proteins