The β1 and β3 integrins promote T cell receptor-mediated cytotoxic T lymphocyte activation

被引:57
作者
Doucey, MA [1 ]
Legler, DF
Faroudi, M
Boucheron, N
Baumgaertner, P
Naeher, D
Cebecauer, M
Hudrisier, D
Rüegg, C
Palmer, E
Valitutti, S
Bron, C
Luescher, IF
机构
[1] Univ Lausanne, Inst Biochem, CH-1066 Epalinges, Switzerland
[2] Univ Lausanne, Ludwig Inst Canc Res, Lausanne Branch, CH-1066 Epalinges, Switzerland
[3] CHU Purpan, INSERM, U563, F-31059 Toulouse, France
[4] Univ Basel, Kantonsspital, CH-4031 Basel, Switzerland
[5] Univ Lausanne, Sch Med, Ctr Pluridisciplinaire Oncol, CH-1066 Epalinges, Switzerland
关键词
D O I
10.1074/jbc.M302709200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Recognition by CD8(+) cytotoxic T lymphocytes (CTLs) of antigenic peptides bound to major histocompatibility class (MHC) I molecules on target cells leads to sustained calcium mobilization and CTL degranulation resulting in perforin-dependent killing. We report that beta(1) and beta(3) integrin-mediated adhesion to extracellular matrix proteins on target cells and/or surfaces dramatically promotes CTL degranulation. CTLs, when adhered to fibronectin but not CTL in suspension, efficiently degranulate upon exposure to soluble MHC . peptide complexes, even monomeric ones. This adhesion induces recruitment and activation of the focal adhesion kinase Pyk2, the cytoskeleton linker paxillin, and the Src kinases Lck and Fyn in the contact site. The T cell receptor, by association with Pyk2, becomes part of this adhesion-induced activation cluster, which greatly increases its signaling.
引用
收藏
页码:26983 / 26991
页数:9
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