T-cell-specific surface glycoprotein CD28 and Cytotoxic T-lymphocyte protein 4 receptors (CD28/CTLA-4)

CD80-related receptors on T cells primarily refer to CD28 and Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA-4), which are critical regulators of the adaptive immune response. CD28 is the primary costimulatory receptor that binds to CD80 (B7-1) and CD86 (B7-2) on antigen-presenting cells, providing the essential second signal for full T-cell activation, proliferation, and survival. Conversely, CTLA-4 is a coinhibitory receptor that binds the same ligands with higher affinity, serving as a key immune checkpoint to dampen immune responses and maintain self-tolerance. These receptors are major therapeutic targets: CTLA-4 inhibitors like ipilimumab are used in cancer immunotherapy to unleash anti-tumor T-cell activity, while CTLA-4-Ig fusion proteins like abatacept are used to treat autoimmune diseases by blocking the CD28 costimulatory pathway. Additionally, recent evidence suggests that CD80 can interact with PD-L1 on T cells, further modulating immune signaling and highlighting the complexity of this regulatory network. The balance between CD28 and CTLA-4 signaling is fundamental to immune homeostasis, and its dysregulation is implicated in various pathologies, including cancer and autoimmunity.

Other names

CD80 receptorsB7-1 receptorsCD28 familyCD28 and CD152T-cell-specific surface glycoprotein CD28Cytotoxic T-lymphocyte-associated protein 4PD-L1

Drugs targeting these receptors modulate T-cell activity by either blocking the costimulatory signal of CD28 to induce immunosuppression, blocking the inhibitory signal of CTLA-4 to enhance anti-tumor immune responses (checkpoint inhibition), or directly activating CD28 to stimulate T-cell activity.