CD80/CD86 (CTLA-4-Ig)

Class

T-cell costimulation modulator

CD80 and CD86 are proteins displayed on antigen-presenting cells, structures that show fragments of foreign or self material to T cells. Full T-cell activation requires two signals: recognition of an antigen fragment by the T-cell receptor, and a second 'costimulatory' signal delivered when CD28 on the T cell binds CD80 or CD86. Without this second signal, T cells fail to activate properly and can become functionally unresponsive. CTLA-4 is a naturally occurring receptor that also binds CD80/CD86, but with higher affinity than CD28, and its engagement dampens T-cell activation rather than promoting it. Fusion proteins built from the CTLA-4 binding domain joined to an antibody-derived scaffold exploit this biology: by occupying CD80/CD86, they prevent CD28 engagement and blunt costimulation broadly across T cells, regardless of the antigen involved. This mechanism is relevant wherever excessive or misdirected T-cell activation drives disease, including autoimmune and inflammatory conditions and immune responses that threaten transplanted organs. Because it acts upstream of antigen specificity, it dampens T-cell responses generally rather than targeting only disease-causing cells, which is both its therapeutic rationale and its principal limitation.