Trans-Endocytosis of CD80 and CD86: A Molecular Basis for the Cell-Extrinsic Function of CTLA-4

被引：1308

作者：

Qureshi, Omar S. ^{[1
]}

Zheng, Yong ^{[1
]}

Nakamura, Kyoko ^{[1
]}

Attridge, Kesley ^{[1
]}

Manzotti, Claire ^{[1
]}

Schmidt, Emily M. ^{[1
]}

Baker, Jennifer ^{[1
]}

Jeffery, Louisa E. ^{[1
]}

Kaur, Satdip ^{[1
]}

Briggs, Zoe ^{[1
]}

Hou, Tie Z. ^{[1
]}

Futter, Clare E. ^{[2
]}

Anderson, Graham ^{[1
]}

Walker, Lucy S. K. ^{[1
]}

Sansom, David M. ^{[1
]}

机构：

[1] Univ Birmingham, Sch Med, Inst Biomed Res, Sch Immun & Infect,MRC,Ctr Immune Regulat, Birmingham B15 2TT, W Midlands, England

[2] UCL, Dept Cell Biol, Inst Ophthalmol, London EC1V 9EL, England

来源：

SCIENCE | 2011年 / 332卷 / 6029期

基金：

英国生物技术与生命科学研究理事会; 英国惠康基金;

关键词：

T-CELL; DENDRITIC CELLS; SURFACE EXPRESSION; TARGET-CELLS; B-CELLS; ACTIVATION; PROTEINS; LYMPHOPROLIFERATION; TROGOCYTOSIS; SECRETION;

D O I：

10.1126/science.1202947

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Cytotoxic T lymphocyte antigen 4 (CTLA-4) is an essential negative regulator of T cell immune responses whose mechanism of action is the subject of debate. CTLA-4 shares two ligands (CD80 and CD86) with a stimulatory receptor, CD28. Here, we show that CTLA-4 can capture its ligands from opposing cells by a process of trans-endocytosis. After removal, these costimulatory ligands are degraded inside CTLA-4-expressing cells, resulting in impaired costimulation via CD28. Acquisition of CD86 from antigen-presenting cells is stimulated by T cell receptor engagement and observed in vitro and in vivo. These data reveal a mechanism of immune regulation in which CTLA-4 acts as an effector molecule to inhibit CD28 costimulation by the cell-extrinsic depletion of ligands, accounting for many of the known features of the CD28-CTLA-4 system.

引用

页码：600 / 603

页数：4

共 31 条

[1] Capture of plasma membrane fragments from target cells by trogocytosis requires signaling in T cells but not in B cells [J].