CD1d is a non-polymorphic, MHC class I-like glycoprotein that plays a crucial role in presenting lipid antigens to invariant natural killer T (iNKT) cells. It is widely expressed in both hematopoietic and non-hematopoietic cells, including professional antigen-presenting cells (APCs), thymocytes, hepatic stellate cells, hepatocytes, adipocytes, and intestinal epithelial cells. Structurally, CD1d consists of a heavy chain with three extracellular domains (伪1, 伪2, and 伪3) that interact non-covalently with beta-2-microglobulin (B2M). The antigen-binding groove of CD1d, formed by two anti-parallel 伪 helices and one anti-parallel 尾 helix, is deeper than that of typical MHC class I molecules and is specialized for binding lipid antigens. CD1d presents a wide range of lipid antigens, including diacylglycerols, phospholipids, glycosphingolipids, ether lipids, and lipopeptides, to CD1d-restricted T cells. This interaction is critical for activating iNKT cells, which have potent immunoregulatory functions and contribute to immune responses against cancer, infections, and autoimmune diseases.
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