CD28 (Cluster of Differentiation 28) (CD28)

CD28 (Cluster of Differentiation 28) is a costimulatory receptor expressed primarily on T cells, essential for their full activation and survival in response to antigen. Its principal ligands, CD80 (B7-1) and CD86 (B7-2), are expressed on antigen-presenting cells. The interaction between CD80/CD86 and CD28 delivers a critical second signal that, together with T cell receptor (TCR) stimulation, triggers T cell proliferation, survival, cytokine production (notably IL-2 and IL-6), and prevention of T cell anergy. This pathway is foundational in adaptive immunity and is a crucial therapeutic target in immuno-oncology (checkpoint inhibition), autoimmunity, and transplantation. The CD28 costimulatory pathway is tightly regulated by inhibitory receptors such as CTLA-4, which competes with CD28 for binding CD80/86 but with higher affinity. Drugs modulating this axis manipulate immune responses for therapeutic benefit but require careful control to avoid severe adverse immune reactions.

Other names

T-cell-specific surface glycoprotein CD28TP44CD28 antigen

Costimulatory receptor antagonism (drugs like abatacept, belatacept bind CD80/CD86 and inhibit CD28 signaling). Immune checkpoint modulation (by blocking or enhancing CD80-CD28 or CD80–CTLA-4 interaction). Agonism (CD28 superagonist antibodies stimulating T cell proliferation).