T-cell-specific surface glycoprotein CD28 (CD28)

CD28 is a cell surface glycoprotein receptor expressed predominantly on T cells which provides an essential co-stimulatory signal required for full T cell activation[1]. Upon engagement by its ligands CD80 (B7-1) and CD86 (B7-2) expressed on antigen-presenting cells, CD28 amplifies TCR signaling, driving gene expression changes that lead to proliferation, differentiation, survival, cytokine secretion, and enhanced effector functions. CD28 is a disulfide-linked homodimer with a structure belonging to the immunoglobulin superfamily, containing extracellular IgV-like domains for ligand binding, and a cytoplasmic tail with tyrosine- and proline-rich signaling motifs[1][2][4][5][7]. The cytoplasmic domain is critical for recruiting SH2- and SH3-domain containing kinases and adaptors such as PI3K, Lck, and Grb2[3][5][7]. In therapeutic contexts, the CD28 signaling domain is utilized in the design of chimeric antigen receptors (CARs) to confer strong costimulatory signals for engineered T-cells, although safety concerns regarding systemic immune activation have limited the direct targeting of CD28 in clinical practice[6][4].

Other names

Cluster of Differentiation 28CD28 molecule

For agents targeting or incorporating the CD28 signaling domain, the mechanism is typically costimulatory signaling via intracellular activation of phosphatidylinositol 3-kinase (PI3K) and other downstream effectors, amplifying T-cell receptor (TCR) signaling for robust T-cell responses[5][7][3].