Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4.

Omar Qureshi, Yong Zheng, Kyoko Nakamura, Kesley Attridge, Claire Manzotti, EM Schmidt, Jennifer Baker, Louisa Jeffery, Satdip Kaur, Zoe Briggs, Tiezheng Hou, CE Futter, Graham Anderson, Lucy Walker, David Sansom

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848 Citations (Scopus)


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 languageEnglish
Pages (from-to)600-3
Number of pages4
Issue number6029
Publication statusPublished - 29 Apr 2011


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