CD80CD86

CD80 and CD86 are membrane-bound co-stimulatory proteins of the B7 family, encoded by the CD80 and CD86 genes. They are expressed mainly on professional antigen-presenting cells, including dendritic cells, macrophages, and B cells, and their expression is upregulated during APC maturation or activation.

In T cell activation, two signals are required: recognition of antigen presented by MHC molecules (signal 1) and a second co-stimulatory signal (signal 2) provided by CD28 on T cells engaging CD80 or CD86 on APCs. Interaction of CD28 with CD80/CD86 promotes T cell proliferation, interleukin-2 production, and survival. Conversely, the inhibitory receptor CTLA-4 (CD152), which is upregulated after T cell activation, also binds CD80 and CD86 with higher affinity, delivering a negative signal that limits T cell responses and supports peripheral tolerance. The balance between CD28-mediated stimulation and CTLA-4–mediated inhibition shapes T cell fate, including activation, differentiation, and regulatory T cell development.

CD86 is typically expressed earlier during the immune response, with CD80 expression increasing later, and together they sustain or modulate T cell responses. Beyond T cells, CD80 and CD86 participate in immune regulation through interactions with other receptors and cell types, contributing to the overall orchestration of adaptive immunity.

Clinical relevance includes therapeutic strategies that target the B7–CD28/CTLA-4 axis. Abatacept, a CTLA-4–Ig fusion protein, binds CD80 and CD86 to block CD28 signaling and is used in autoimmune diseases. CTLA-4–targeted antibodies, such as ipilimumab, enhance anti-tumor immunity by disrupting CTLA-4–mediated inhibition.