T-cell surface glycoprotein CD28 (CD28)

CD28 is a pivotal co-stimulatory receptor constitutively expressed on the surface of T-cells, belonging to the immunoglobulin superfamily. It provides the essential second signal required for full T-cell activation and survival upon binding its ligands, CD80 (B7-1) and CD86 (B7-2), on antigen-presenting cells (APCs). Without CD28-mediated co-stimulation, T-cell receptor (TCR) engagement by an antigen often leads to T-cell anergy or apoptosis rather than an effective immune response (UniProt P10747; PubMed: 24703777). In therapeutic contexts, CD28 is a major target for treating autoimmune disorders and preventing transplant rejection. Drugs like Abatacept and Belatacept function as CTLA-4-Ig fusion proteins that competitively bind to CD80/CD86, thereby preventing CD28 engagement and dampening overactive immune responses (StatPearls: NBK535422). Conversely, the intracellular signaling domain of CD28 is a critical component of second-generation chimeric antigen receptor (CAR) T-cell therapies, where it enhances the proliferation and persistence of engineered cells against tumors. A notable safety challenge in targeting CD28 was highlighted by the Theralizumab (TGN1412) trial, where a superagonistic antibody caused life-threatening cytokine storms, emphasizing the need for precise modulation of this pathway (PubMed: 22013006).

Other names

Cluster of Differentiation 28TP44T-cell-specific surface glycoprotein CD28

Competitive inhibition of CD28/B7 interaction; Agonism (experimental); Signaling domain integration in CAR-T cells