T-cell surface glycoprotein CD1d (CD1d)

T-cell surface glycoprotein CD1d is a non-polymorphic, MHC class I-like molecule that specializes in presenting lipid and glycolipid antigens to invariant natural killer T (iNKT) cells [1, 3]. Unlike classical MHC molecules that present peptides, CD1d features a deep hydrophobic binding groove tailored to accommodate the hydrocarbon chains of lipids [3, 6]. Upon binding a lipid ligand, the CD1d-lipid complex is recognized by the semi-invariant T-cell receptor of iNKT cells, triggering a rapid and massive release of cytokines such as IFN-gamma and IL-4 [5, 12]. This unique function allows CD1d to bridge the innate and adaptive immune systems, making it a critical regulator of immune responses in cancer, infection, and autoimmunity [11, 18]. In oncology, CD1d agonists like alpha-galactosylceramide are used to stimulate anti-tumor immunity, although challenges such as iNKT cell anergy and cytokine-related toxicities remain [2, 8]. Conversely, CD1d antagonism or modulation is being explored for treating autoimmune and inflammatory conditions where overactive iNKT cells contribute to pathology [7, 15].

Other names

CD1DR3R3G1Antigen-presenting glycoprotein CD1d

CD1d agonists bind to the CD1d molecule on antigen-presenting cells, forming a complex that is recognized by the T-cell receptor of iNKT cells to trigger activation and cytokine release; CD1d antagonists block this interaction to dampen immune responses.