T Cell Receptor "inside-out" Pathway Via Signaling Module SKAP1-RapL Regulates T Cell Motility and Interactions in Lymph Nodes

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2010 Mar 30

PMID 20346707

Citations 76

Authors

Monika Raab

Hongyan Wang

Yuning Lu

Xin Smith

Zhonglin Wu

Klaus Strebhardt

John E Ladbury

Christopher E Rudd

Affiliations

Soon will be listed here.

Abstract

Although essential for T cell function, the identity of the T cell receptor "inside-out" pathway for lymphocyte function-associated antigen 1 (LFA-1) adhesion has proved elusive. Here, we define the "inside-out" pathway mediated by N-terminal SKAP1 (SKAP-55) domain binding to the C-terminal SARAH domain of RapL. TcR induced Rap1-RapL complex formation and LFA-1 binding failed to occur in Skap1(-/-) primary T cells. SKAP1 generated a SKAP1-RapL-Rap1 complex that bound to LFA-1, whereas a RapL mutation (L224A) that abrogated SKAP1 binding without affecting MST1 disrupted component colocalization in vesicles as well as T cell-dendritic cell (DC) conjugation. RapL expression also "slowed" T cell motility in D011.10 transgenic T cells in lymph nodes (LNs), an effect reversed by the L224A mutation with reduced dwell times between T cells and DCs. Overall, our findings define a TCR "inside-out" pathway via N-SKAP1-C-RapL that regulates T cell adhesion, motility, and arrest times with DCs in LNs.

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