Role for the Abi/wave protein complex in T cell receptor-mediated proliferation and cytoskeletal remodeling

Curr Biol. 2006 Jan 10;16(1):35-46. doi: 10.1016/j.cub.2005.12.024.


Background: The molecular reorganization of signaling molecules after T cell receptor (TCR) activation is accompanied by polymerization of actin at the site of contact between a T cell and an antigen-presenting cell (APC), as well as extension of actin-rich lamellipodia around the APC. Actin polymerization is critical for the fidelity and efficiency of the T cell response to antigen. The ability of T cells to polymerize actin is critical for several steps in T cell activation including TCR clustering, mature immunological synapse formation, calcium flux, IL-2 production, and proliferation. Activation of the Rac GTPase has been linked to regulation of actin polymerization after TCR stimulation. However, the molecules required for TCR-mediated actin polymerization downstream of activated Rac have remained elusive. Here we identify a novel role for the Abi/Wave protein complex, which signals downstream of activated Rac, in the regulation of actin polymerization and T cell activation in response to TCR stimulation.

Results: Here we show that Abi and Wave rapidly translocate from the T cell cytoplasm to the T cell:B cell contact site in the presence of antigen. Abi and Wave colocalize with actin at the T cell:B cell conjugation site. Moreover, Wave and Abi are necessary for actin polymerization after T cell activation, and loss of Abi proteins in mice impairs TCR-induced cell proliferation and IL-2 production in primary T cells. Significantly, the impairment in actin polymerization in cells lacking Abi proteins is due to the inability of Wave proteins to localize to the T cell:B cell contact site in the presence of antigen, rather than the destabilization of the components of the Wave protein complex.

Conclusions: The Abi/Wave complex is a novel regulator of TCR-mediated actin dynamics, IL-2 production, and proliferation.

Publication types

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

MeSH terms

  • Actins / metabolism
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / physiology*
  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / physiology
  • Cell Proliferation
  • Cytoskeletal Proteins
  • Cytoskeleton / metabolism*
  • Cytoskeleton / ultrastructure
  • Extracellular Space / chemistry
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / physiology
  • Humans
  • Interleukin-2 / immunology
  • Interleukin-2 / metabolism
  • Jurkat Cells
  • Mice
  • Models, Biological
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / ultrastructure
  • Wiskott-Aldrich Syndrome Protein Family / analysis
  • Wiskott-Aldrich Syndrome Protein Family / physiology*


  • ABI1 protein, human
  • Abi1 protein, mouse
  • Abi2 protein, mouse
  • Actins
  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • Homeodomain Proteins
  • Interleukin-2
  • Receptors, Antigen, T-Cell
  • WASF1 protein, human
  • WASF2 protein, human
  • Wiskott-Aldrich Syndrome Protein Family