Projects per year
Abstract
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.
Original language | English |
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Pages (from-to) | 600-3 |
Number of pages | 4 |
Journal | Science |
Volume | 332 |
Issue number | 6029 |
DOIs | |
Publication status | Published - 29 Apr 2011 |
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Dive into the research topics of 'Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4.'. Together they form a unique fingerprint.Projects
- 4 Finished
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Generation of Intrathymic Microenvironments to Establish T-Cell Tolerance
Anderson, G., Jenkinson, E. & Lane, P.
1/10/10 → 30/09/15
Project: Research Councils
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What is the Molecular Basis of CTLA-4 Trans-Endocytosis?
Sansom, D. & Walker, L.
Biotechnology & Biological Sciences Research Council
1/05/10 → 30/04/14
Project: Research Councils
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MRC Centre For Immune Regulation (Linked to DCDF.RRAK10540) (Linked to 14810 & 14835)
Jenkinson, E.
3/08/09 → 30/09/17
Project: Research Councils
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What is the Function of CTLA-4 Endocytosis?
Sansom, D. & Walker, L.
Biotechnology & Biological Sciences Research Council
1/07/06 → 30/06/09
Project: Research Councils