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CD1 is a family of atypical MHC class I molecules that present various endogenous and exogenous lipid antigens to CD1‐restricted T cells. While little is known about the function of CD1a‐, CD1b‐, and CD1c‐restricted lipid‐reactive T cells due to their absence in mice, CD1d‐restricted natural killer T (NKT) cells have been extensively studied since their description almost 20 years ago. NKT cells, effector memory cells that share characteristics of innate and adaptive lymphocytes, are among the earliest responders in immune reactions and have broad effects on the activation of other immune cell lineages, including NK cells, T cells, and B cells. Accordingly, studies in mice have revealed critical roles of NKT cells in infectious, malignant, and autoimmune diseases. The recent description of primary immunodeficiencies associated with defects in CD1 and CD1‐restricted T cells has provided a unique opportunity to study the biological role of lipid antigen presentation in human disease. Intriguingly, these studies revealed that defects in lipid immunity are associated with susceptibility to selected infectious and malignant diseases but not with broad immunodeficiency.
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