Vav1 controls integrin clustering and MHC/peptide-specific cell adhesion to antigen-presenting cells.
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.
Krawczyk
Connie
C
Amgen Institute, 620 University Avenue, Toronto, Ontario M5G 2C1, Canada.
Oliveira-dos-Santos
Antonio
A
Sasaki
Takehiko
T
Griffiths
Emily
E
Ohashi
Pamela S
PS
Snapper
Scott
S
Alt
Fred
F
Penninger
Josef M
JM
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D002448:Cell Adhesion / Q000276:immunology / Q000502:physiology; D018797:Cell Cycle Proteins; D016023:Integrins / Q000502:physiology*; D008211:Lymphocyte Cooperation / Q000235:genetics; D008285:Major Histocompatibility Complex / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D011506:Proteins / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D051316:Wiskott-Aldrich Syndrome Protein
D018797:Cell Cycle Proteins; D016023:Integrins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell; C496619:Vav1 protein, mouse; C495768:Was protein, mouse; D051316:Wiskott-Aldrich Syndrome Protein