CD28 and CTLA-4 Immunoregulatory Axis (CD28/CTLA-4)

CD28 and CTLA-4 are homologous transmembrane glycoproteins expressed on T cells and belonging to the immunoglobulin superfamily. CD28 is present on most resting and activated T cells, acting as a major co-stimulatory receptor for T-cell activation upon binding B7 molecules (CD80/CD86) presented by antigen-presenting cells. CTLA-4 is upregulated following T-cell activation and is constitutively expressed on regulatory T cells, where it serves as a critical coinhibitory receptor. CTLA-4 binds B7 molecules with much higher affinity and avidity than CD28, outcompeting CD28 for these ligands and thereby dampening T-cell responses. The regulatory balance between CD28-mediated activation and CTLA-4-mediated inhibition is fundamental to normal immune homeostasis and tolerance. Therapeutically, blocking CTLA-4 (e.g., with ipilimumab) activates antitumor immunity but may provoke autoimmunity. Fusion proteins based on CTLA-4 (e.g., abatacept, belatacept) are used to suppress immune activation in autoimmunity and transplantation. Abnormalities in CTLA-4 expression or function are linked to autoimmune conditions; conversely, excessive CD28 signaling can drive inflammation.

Other names

T-cell-specific surface glycoprotein CD28CD152CTLA4

CTLA-4 blockers inhibit CTLA-4, release inhibitory checkpoint, and enhance T-cell activation. CTLA-4-Ig fusion proteins compete with CD28 for B7 ligands, inhibiting T-cell activation. Anti-CD28 antibodies stimulate or modulate T-cell co-stimulation.