The Wiskott-Aldrich syndrome protein acts downstream of CD2 and the CD2AP and PSTPIP1 adaptors to promote formation of the immunological synapse

Immunity. 2003 Jan;18(1):141-54. doi: 10.1016/s1074-7613(02)00516-2.


The Wiskott-Aldrich syndrome protein (WASp) couples actin cytoskeletal rearrangement to T cell activation, but the mechanisms involved are unknown. Here, we show that antigen-induced formation of T cell:APC conjugates and synapses is abrogated in WASp-deficient T cells and that CD2 engagement evokes interactions between the proline-rich region required for WASp translocation to the synapse and the PSTPIP1 adaptor SH3 domain and between the PSTPIp1 coiled-coil domain and both CD2 and another CD2-binding adaptor, CD2AP. The induced colocalization of these proteins at the synapse is disrupted by expression of coiled-coil domain-deleted PSTPIP1. These data, together with the impairment in CD2-induced actin polymerization observed in WASp-deficient cells, suggest that PSTPIP1 acts downstream of CD2/CD2AP to link CD2 engagement to the WASp-evoked actin polymerization required for synapse formation and T cell activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • CD2 Antigens / metabolism*
  • Carrier Proteins / immunology*
  • Carrier Proteins / metabolism*
  • Cytoskeletal Proteins / immunology*
  • Cytoskeletal Proteins / metabolism*
  • Cytoskeleton / immunology
  • Cytoskeleton / metabolism
  • Humans
  • Jurkat Cells
  • Lymphocyte Activation
  • Membrane Microdomains / immunology
  • Membrane Microdomains / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Proteins / immunology*
  • Proteins / metabolism*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Wiskott-Aldrich Syndrome / immunology*
  • Wiskott-Aldrich Syndrome / metabolism*
  • Wiskott-Aldrich Syndrome Protein
  • src Homology Domains


  • Actins
  • Adaptor Proteins, Signal Transducing
  • CD2 Antigens
  • CD2-associated protein
  • Carrier Proteins
  • Cytoskeletal Proteins
  • PSTPIP1 protein, human
  • Proteins
  • Pstpip1 protein, mouse
  • WAS protein, human
  • Was protein, mouse
  • Wiskott-Aldrich Syndrome Protein