CD1d is a non-polymorphic MHC class I-like glycoprotein that presents lipid and glycolipid antigens to invariant natural killer T (iNKT) cells 1. CD1d binds both self-lipids and microbial glycolipids through a conformational binding groove, with the sphingosine chain anchored in the C' pocket and acyl chains in the A' pocket 2. Upon antigen binding, CD1d undergoes conformational changes that facilitate iNKT TCR recognition 3. iNKT cells recognize CD1d-presented antigens through semi-invariant αβ TCRs and initiate rapid innate-like immune responses, including IL-4, IL-13, and IFN-γ production, bridging innate and adaptive immunity 45. This CD1d-iNKT axis regulates diverse immunological processes including antimicrobial responses against bacteria and parasites, as well as tumor immunity 15. CD1d expression on B cells and other antigen-presenting cells enables cognate interactions with iNKT cells 1. Altered CD1d expression serves as an immune evasion mechanism in viral infections and malignancies 6. The CD1d-iNKT axis represents a therapeutic target, with synthetic lipid antigens showing promise as vaccine adjuvants and immunotherapeutic agents 45.