Antigen-presenting glycoprotein CD1d (CD1d) (CD1d)

Antigen-presenting glycoprotein CD1d (CD1d) is a non-polymorphic, MHC class I-like transmembrane protein that specializes in the presentation of lipid and glycolipid antigens to natural killer T (NKT) cells [1, 10]. Unlike classical MHC molecules that present peptide fragments, CD1d possesses a deep hydrophobic binding pocket capable of sequestering various lipid species, including sphingolipids and glycerolipids of both endogenous and microbial origin [1, 12]. Upon presentation of these lipids, CD1d interacts with the semi-invariant T-cell receptor of invariant NKT (iNKT) cells, triggering a rapid and potent release of both Th1 and Th2 cytokines, such as interferon-gamma and interleukin-4 [7, 10]. This unique function allows CD1d to act as a critical bridge between the innate and adaptive immune systems, modulating responses to infections, tumors, and autoantigens [10, 13]. In oncology, CD1d is a target for synthetic agonists like alpha-galactosylceramide, which aim to harness NKT cell-mediated anti-tumor immunity, while its downregulation by certain viruses and cancers serves as a mechanism for immune evasion [7, 12]. Therapeutic development also explores CD1d blockade or modulation to treat autoimmune and inflammatory conditions where NKT cell activity may be pathogenic [2, 10].

Other names

CD1DR3G1CD1d moleculeT-cell surface glycoprotein CD1dThymocyte antigen CD1DCD1 antigen-like family member D

CD1d agonists bind to the CD1d molecule on antigen-presenting cells, facilitating the presentation of lipid antigens to the T-cell receptor of invariant natural killer T (iNKT) cells, which leads to their activation and subsequent cytokine release [2, 8]. Alternatively, anti-CD1d monoclonal antibodies can block the interaction between CD1d and NKT cells to modulate immune responses in autoimmune or inflammatory contexts [7, 10].