CD2 is a transmembrane glycoprotein and one of the earliest T cell markers. It is widely expressed on the surface of human immune cells, including T cells, natural killer cells (NK cells), some B cells, and monocytes. It participates in the co-stimulatory pathway of T cell activation and plays a key role in the interaction and signaling between immune cells.
(Data source: Ho P, et al. Cancer Cell. 2023)
CD2 structure:
CD2 consists of 327 amino acids (including the signal sequence) and is approximately 40 kDa. Fully glycosylated CD2 can reach 50 kDa. The extracellular domain (ECD, 25-209) of CD2 consists of two Ig-like domains connected by transmembrane helices to a disordered, proline-rich cytoplasmic tail. The membrane-proximal domain of the CD2 ECD connects the adhesion (membrane-distal) domain to the cell membrane and may be involved in CD2 aggregation following T cell activation. The membrane -distal domain is responsible for binding to LFA3 (also known as CD58), while the intracellular segment contains five potential SRC homology 3 domain (Sh3) binding sites.
(Data source: Binder C, et al. Front Immunol. 2020)
CD2 signaling pathway and regulation:
CD2 is a contact zone for stable cell-cell interactions between T cells and antigen-presenting cells. It is composed of a supramolecular activation cluster (SMAS), with a central cSMAC surrounded by a peripheral pSMAC, which in turn is surrounded by a distal dSMAC. The CD2/LFA3 complex cluster forms a ring structure between the dSMAC and pSMAC. Within the cell, CD2 influences the rearrangement of the actin cytoskeleton and stimulates cell signaling, regulating thymocyte development and T cell activation.
(Data source Binder C, et al. Front Immunol. 2020)
CD2 Therapeutic Applications:
Due to its crucial role in immune cell interactions and signaling, the CD2 protein has become a potential target for the study and treatment of immune-related diseases. Characterized by overactivation of T and NK cells, CD2-LFA3 could serve as a natural target for the treatment of organ transplantation and certain autoimmune disorders, potentially inducing and maintaining immunosuppression, prolonging graft survival, and reducing the risk of graft rejection or autoimmune inflammation.
(Data source Ellis CN, et al. N Engl J Med. 2001)
