In addition to the classical MHC class I and class II molecules, human intestinal epithelial cells also express nonclassical MHC class I-like molecules on their cell surface. CD1d is a non polymorphic MHC-like molecule whose expression is mainly localized to the epithelial cells of the gastrointestinal tract. The biochemical structure of CD1d on intestinal epithelial cells (IECs) exists in two forms: a 37-kD nonglycosylated, ƒÀ2-microglobulin(ƒÀ2M) independent and a 48-kD glycosylated, ƒÀ2 M dependent form. Immunolocalization studies suggest that the 37-kD nonglycosylated form of CD1d is limited to the apical cell surface whereas the 48-50-kD glycosylated, ƒÀ2M dependent form of CD1d is expressed both on the apical and the basolateral surfaces. The ƒÀ2M association with CD1d seems to be important in regulating the pattern of glycosylation and the localization of CD1d within the cell based upon studies of the structure of CD1d in a transfected model cell line and in polarized epi thelial cell monolayers. The functional role of intestinal CD1d remains unknown. However, based upon in vitro studies of the antigens presented by human CD1d and mouse CD1d, CD1d expressed on IECs likely presents a very hydrophobic glycolipid molecule possibly from the cell wall of bacteria or host cells. The processed-lipid antigen presented by CD1d may then involve a yet-to-be-identified subpopulation of the resident, oligoclonal ƒ¿ ƒÀ TCR CD8-intestinal intraepithelial lymphocyte(iIEL) T cells. Subsequently, these T cells would be very important in regulating the local immune response by producing cytokines and recruiting other immune modulating cells to destroy infected cells, regenerate normal IECs, and possibly downregulate activated T cells to maintain mucosal integrity.(Keio J Med 50 (1): 39-44, March 2001)