T-cell-specific surface glycoprotein CD28 intracellular domain (CD28 ICD)

The CD28 intracellular costimulatory domain is the cytoplasmic portion of the CD28 receptor, which is essential for providing the second signal required for full T-cell activation (UniProt P10747). This domain contains critical signaling motifs, including a YMNM motif that recruits phosphoinositide 3-kinase (PI3K) and proline-rich regions that bind to Grb2 and Gads, facilitating the activation of the Akt and NF-kappaB pathways (PubMed: 29902341). In clinical practice, this domain is most prominently used as a signaling component in second-generation Chimeric Antigen Receptor (CAR) T-cell therapies, such as Axicabtagene ciloleucel (PubMed: 31003464). By integrating the CD28 intracellular domain into CAR constructs, researchers can trigger rapid T-cell proliferation and potent effector functions upon antigen recognition. However, the use of this domain is associated with specific therapeutic challenges, including a higher propensity for T-cell exhaustion and an increased risk of severe cytokine release syndrome compared to other costimulatory domains like 4-1BB (PubMed: 30206144). Consequently, it remains a focal point for engineering more controlled and persistent immune responses in the treatment of hematologic malignancies and solid tumors.

Other names

CD28 cytoplasmic tailCD28 signaling domainCD28 endodomainCD28 cytoplasmic domain

Provides costimulatory signaling through the recruitment of PI3K and Grb2, activating the Akt and NF-kappaB pathways to enhance T-cell effector function and survival.