摘要
In a recent issue of Nature Immunology,Kennedy et al.reported that CTLA-4(CD152)differentially targets two distinct ligands,CD80 and CD86,on antigen-presenting cells(APCs)for destruction or recycling following transendocytosis(TE),resulting in separate fates for CTLA-4 on T_(reg) cells and thereby regulating autoimmunity.Mechanistically,whereas CTLA-4 tightly binds CD80 for TE and causes ubiquitination and trafficking to late endosomes and lysosomes for degradation,CTLA-4 weakly binds CD86 for TE,resulting in dissociation under acidic conditions(pH<6)and recycling of CTLA-4 to the plasma membrane for further CD86 removal.Therefore,CD86 targeting by CTLA-4 regulates T-cell function in autoimmunity[1]and presumably immune surveillance of cancer cells(Fig.1).
