T-lymphocyte activation antigen CD80 and CD86 (CD80/CD86)

CD80 (B7-1) and CD86 (B7-2) are critical costimulatory receptors expressed on the surface of antigen-presenting cells (APCs), including dendritic cells and macrophages (UniProt P33681, P42081). They provide the necessary secondary signal for T-cell activation by binding to CD28 on the T-cell surface. However, they also interact with the inhibitory receptor CTLA-4, which binds with higher affinity and suppresses T-cell responses (Science, 2011, 332(6030):600-603). The therapeutic approach involving exosomal CTLA-4 utilizes extracellular vesicles to deliver CTLA-4 to APCs, where it can bind and internalize CD80/CD86 through transendocytosis, thereby inducing immune tolerance (Journal of Biological Chemistry, 2016, 291(12):6545-6557). This mechanism is particularly relevant for treating autoimmune diseases and preventing transplant rejection by effectively stripping APCs of their costimulatory capacity. In contrast, blocking the CTLA-4/CD80/CD86 axis with monoclonal antibodies is a cornerstone of cancer immunotherapy, aimed at enhancing the body's immune response against tumors (Nature Reviews Cancer, 2012, 12:252-264).

Other names

B7-1B7-2B7.1B7.2CD28LG1CD28LG2LAB7

Exosomal CTLA-4 binds to CD80 and CD86 on antigen-presenting cells, leading to their downregulation or removal via transendocytosis, which prevents CD28-mediated T-cell costimulation.