CD80 and CD86 (B7-1 and B7-2) (CD80/CD86)

CD80 (B7-1) and CD86 (B7-2) are critical costimulatory ligands expressed on the surface of antigen-presenting cells (APCs), such as dendritic cells and B cells. They play a dual role in the immune system by binding to the stimulatory receptor CD28 to promote T cell activation or to the inhibitory receptor CTLA-4 to suppress it. CTLA-4 has a significantly higher affinity for these ligands than CD28, allowing it to competitively inhibit costimulation. In the specific context of iG-Tregs (induced HLA-G+ regulatory T cells), these cells utilize surface-expressed CTLA-4 to actively downregulate or physically remove CD80 and CD86 from APCs via a process known as trans-endocytosis or trogocytosis. This mechanism effectively strips the APCs of their ability to activate effector T cells, thereby serving as a potent pathway for maintaining peripheral tolerance and preventing conditions like graft-versus-host disease (GvHD). Therapeutic interventions targeting this axis include CTLA-4-Ig fusion proteins like abatacept and belatacept, as well as emerging adoptive cell therapies using pharmacologically induced iG-Tregs.

Other names

B7-1B7-2CD28LG1CD28LG2B7.1B7.2T-lymphocyte activation antigen CD80T-lymphocyte activation antigen CD86

The target molecules CD80 and CD86 are downregulated or removed from the surface of antigen-presenting cells (APCs) through interaction with CTLA-4 expressed on regulatory T cells, such as iG-Tregs. This process prevents these ligands from binding to the stimulatory receptor CD28 on effector T cells, thereby inhibiting T cell activation and promoting immune tolerance.