The vav exchange factor is an essential regulator in actin-dependent receptor translocation to the lymphocyte–antigen-presenting cell interface

^§Howard Hughes Medical Institute, ^*Department of Microbiology and Immunology, and ^¶Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305

Contributed by Mark M. Davis

Abstract

During the interaction of a T cell with an antigen-presenting cell (APC), several receptor ligand pairs, including the T cell receptor (TCR)/major histocompatibility complex (MHC), accumulate at the T cell/APC interface in defined geometrical patterns. This accumulation depends on a movement of the T cell cortical actin cytoskeleton toward the interface. Here we study the involvement of the guanine nucleotide exchange factor vav in this process. We crossed 129 vav^−/− mice with B10/BR 5C.C7 TCR transgenic mice and used peptide-loaded APCs to stimulate T cells from the offspring. We found that the accumulation of TCR/MHC at the T cell/APC interface and the T cell actin cytoskeleton rearrangement were clearly defective in these vav^+/− mice. A comparable defect in superantigen-mediated T cell activation of T cells from non-TCR transgenic 129 mice was also observed, although in this case it was more apparent in vav^−/− mice. These data indicate that vav is an essential regulator of cytoskeletal rearrangements during T cell activation.

Footnotes

↵ † C.W. and A.B. contributed equally to this work.
↵ ‡ Present address: Center for Immunology and Department of Cell Biology, University of Texas, Southwestern Medical Center, Dallas, TX 75390-9093.
↵ ‖ To whom reprint requests should be addressed to: Howard Hughes Medical Institute, Beckman Center, Room B221, Stanford University, Stanford, CA 94305-5428. E-mail: mdavis{at}cmgm.stanford.edu.
Abbreviations:

APC,

antigen-presenting cell;

TCR,

T cell receptor;

MHC,

major histocompatibility complex;

GFP,

green fluorescent protein;

SEA and SEE,

staphylococcal superantigen A and E;

MCC,

moth cytochrome c