细胞生物学
生物
MHC II级
免疫突触
MHC I级
抗原呈递
抗原
动力蛋白
CD8型
效应器
T细胞
主要组织相容性复合体
免疫学
免疫系统
T细胞受体
微管
作者
Anna M. Keller,Tom A. Groothuis,Elise A. M. Veraar,Marije Marsman,Lucas J. Maillette de Buy Wenniger,Hans Janßen,Jacques Neefjes,Jannie Borst
标识
DOI:10.1073/pnas.0700946104
摘要
TNF family member CD70 is the ligand of CD27, a costimulatory receptor that shapes effector and memory T cell pools. Tight control of CD70 expression is required to prevent lethal immunodeficiency. By selective transcription, CD70 is largely confined to activated lymphocytes and dendritic cells (DC). We show here that, in addition, specific intracellular routing controls its plasma membrane deposition. In professional antigen-presenting cells, such as DC, CD70 is sorted to late endocytic vesicles, defined as MHC class II compartments (MIIC). In cells lacking the machinery for antigen presentation by MHC class II, CD70 travels by default to the plasma membrane. Introduction of class II transactivator sufficed to reroute CD70 to MIIC. Vesicular trafficking of CD70 and MHC class II is coordinately regulated by the microtubule-associated dynein motor complex. We show that when maturing DC make contact with T cells in a cognate fashion, newly synthesized CD70 is specifically delivered via MIIC to the immunological synapse. Therefore, we propose that routing of CD70 to MIIC serves to coordinate delivery of the T cell costimulatory signal in time and space with antigen recognition.
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