期刊
JOURNAL OF IMMUNOLOGY
卷 184, 期 10, 页码 5485-5492出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0902219
关键词
-
类别
资金
- Fondation de France [Engt 2006-005656, 2008-002724]
- Fondation pour la Recherche Medicate [DCV20070409268, FDT20071211595]
- Agence Nationale de la Recherche
- Ministere Affaires Etrangeres [63651 IF]
- Groupe de Reflexion sur Is Recherche Cardio-Vasculaire et la Federation Francaise de Cardiologie
CD31 is a transmembrane molecule endowed with T cell regulatory functions owing to the presence of 2 immunotyrosine-based inhibitory motifs. For reasons not understood, CD31 is lost by a portion of circulating T lymphocytes, which appear prone to uncontrolled activation. In this study, we show that extracellular T cell CD31 comprising Ig-like domains 1 to 5 is cleaved and shed from the surface of human T cells upon activation via their TCR. The shed CD31 can be specifically detected as a soluble, truncated protein in human plasma. CD31 shedding results in the loss of its inhibitory function because the necessary cis-homo- oligomerization of the molecule, triggered by the trans-homophilic engagement of the distal Ig-like domain 1, cannot be established by CD31(shed) cells. However, we show that a juxta-membrane extracellular sequence, comprising part of the domain 6, remains expressed at the surface of CD31(shed) T cells. We also show that the immunosuppressive CD31 peptide aa 551-574 is highly homophilic and possibly acts by homo-oligomerizing with the truncated CD31 remaining after its cleavage and shedding. This peptide is able to sustain phosphorylation of the CD31 ITIM686 and of SHP2 and to inhibit TCR-induced T cell activation. Finally, systemic administration of the peptide in BALB/c mice efficiently suppresses Ag-induced T cell-mediated immune responses in vivo. We conclude that the loss of T cell regulation caused by CD31 shedding driven by TCR stimulation can be rescued by molecular tools able to engage the truncated juxta-membrane extracellular molecule that remains exposed at the surface of CD31(shed) cells. The Journal of Immunology, 2010,184: 5485-5492.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据