T-lymphocyte-specific antigen CD28 (CD28)

T-lymphocyte-specific antigen CD28 is a cell-surface **costimulatory receptor** that is essential for full activation of naïve T cells. Expressed constitutively on most CD4+ and about half of CD8+ T cells, CD28 binds to its ligands CD80 (B7.1) and CD86 (B7.2) presented on antigen-presenting cells, delivering a critical second signal that complements T-cell receptor (TCR) engagement. This co-stimulatory signal prevents T cell anergy, promotes T-cell proliferation, survival, cytokine secretion (notably IL-2, IL-6), and supports the downstream differentiation of effector and regulatory T cells[1][2][3][5]. CD28 is a **homodimeric transmembrane glycoprotein** and member of the immunoglobulin superfamily; its cytoplasmic tail contains essential signaling motifs for recruitment of key kinases (Lck, Fyn), adapter proteins (GRB2, GADS), and PI3-kinase, triggering activation pathways that interface with TCR signals[1][3]. Therapeutic targeting of CD28 has been explored in cancer, autoimmune diseases, and transplantation. CD28 agonist treatments carry significant safety concerns due to risk of cytokine release syndrome. Loss of CD28 on T cells (especially CD8+ memory populations) marks aging and chronic disease states, while its persistent expression is essential for initial immune responses but dispensable for antigen-experienced cytotoxic memory cells[2][5]. In summary, CD28 is a **central regulator** of T-cell activation, immune response, and an established therapeutic target with well-documented challenges and opportunities in immunomodulatory drug development.

Other names

Cluster of Differentiation 28CD28 antigenT-cell-specific surface glycoprotein CD28Costimulatory molecule CD28

Agonist antibodies (enhance CD28 signaling to activate T cells); Antagonists or inhibitory agents (block CD28 to suppress T-cell activation); Agents preventing CD28 homodimerization (inhibit signaling).