Vav1 controls integrin clustering and MHC/peptide-specific cell adhesion to antigen-presenting cells

Immunity. 2002 Mar;16(3):331-43. doi: 10.1016/s1074-7613(02)00291-1.

Abstract

Integrin-mediated adhesion is essential for the formation of stable contacts between T cells and antigen-presenting cells (APCs). We show that Vav1 controls integrin-mediated adhesion of thymocytes and T cells to ECM proteins and ICAM1 following TCR stimulation. In a peptide-specific system, Vav1 is required for T cell adhesion to peptide-loaded APCs. Intriguingly, TCR-induced cell adhesion and aggregation of integrins occurs independent of WASP. Whereas LFA-1 and actin caps colocalize in wasp(-/-) T cells in response to TCR stimulation, loss of WASP uncouples TCR caps from actin patches. Our data reveal a novel role for Vav1 and WASP in the regulation of TCR-induced integrin clustering and cell adhesion and show that integrin and TCR clustering are controlled by distinct pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation* / genetics
  • Cell Adhesion / immunology
  • Cell Adhesion / physiology
  • Cell Cycle Proteins*
  • Integrins / physiology*
  • Lymphocyte Cooperation / genetics
  • Major Histocompatibility Complex / physiology
  • Mice
  • Mice, Knockout
  • Proteins / physiology*
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-vav
  • Receptors, Antigen, T-Cell / physiology
  • Wiskott-Aldrich Syndrome Protein

Substances

  • Cell Cycle Proteins
  • Integrins
  • Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-vav
  • Receptors, Antigen, T-Cell
  • Vav1 protein, mouse
  • Was protein, mouse
  • Wiskott-Aldrich Syndrome Protein