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SLP ‐76 is required for optimal CXCR 4‐stimulated T lymphocyte firm arrest to ICAM ‐1 under shear flow
Author(s) -
Lee Dooyoung,
Kim Jiyeon,
Baker Rebecca G.,
Koretzky Gary A.,
Hammer Daniel A.
Publication year - 2012
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201142303
Subject(s) - microbiology and biotechnology , biology , t cell receptor , chemokine receptor , t cell , chemokine , integrin , stromal cell , receptor , immunology , immune system , cancer research , biochemistry
Rapid arrest of T cells at target sites upon engagement of chemokine receptors is crucial to the proper functioning of the immune system. Although T ‐cell arrest always occurs under hydrodynamic forces in vivo, most studies investigating the molecular mechanisms of arrest have been performed under static conditions. While the requirement of the adapter protein SLP ‐76 ( S rc homology 2‐domain containing leukocyte‐specific phosphoprotein of 76 kDa) in TCR ‐induced integrin activation has been demonstrated, its role in chemokine‐triggered T ‐cell adhesion is unknown. Using a flow chamber system, we show that SLP ‐76 plays an important role in regulating the transition from tethering and rolling to firm adhesion of T cells under physiological shear flow in response to CXCL 12α (stromal cell‐derived factor‐1α); SLP ‐76‐deficient primary T cells exhibited defective adhesion with a significant decrease in the number of firmly arrested cells. We further demonstrate the N ‐terminal phosphotyrosines of SLP ‐76 play a critical role in T ‐cell adhesion under flow. These findings reveal a novel role for SLP ‐76 in CXCR 4‐mediated T lymphocyte trafficking.