CD1 IN INTESTINE AND LIVER

University Of California San Diego, La Jolla CA

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Abstract

DESCRIPTION (taken from application) The classic major histocompatibility complex (MHC) class I and class II pathways are well established in antigen presentation. In addition, the CD1 family of proteins are now recognized to likely represent another class of molecules that are important in unique aspects of antigen processing and activation of distinct subsets of T-cells such as those contained within the gut and liver. Human CD1 consists of 5 genes (CD1AE) that are encoded on chromosome 1 outside the MHC locus. Human CDI has strong structural similarities to MHC class I but also shows several features in common with MHC class II, suggesting a distinct relationship to both of the previously characterized classical MHC molecules. CDld, a member of this family, is prominently displayed on intestinal epithelial cells (IEC) and hepatocytes. Furthermore, the expression of CDld is increased in immune-mediated gastrointestinal diseases, such as inflammatory bowel disease and celiac disease. Although the exact role of CDld in the mucosal immune system is unclear, CD1 d exhibits unique biochemical properties and functional characteristics. CDld is expressed on the cell surface of normal IECs as a 37-kD, nonglycosylated molecule independently of pi2-microglobulin which is clearly distinct from all other MHC class I-related molecules. In addition, this biochemical form of CD1d is directly involved in the proliferation of T-cells to normal IECs. In order to understand the function of this unique antigen-presenting molecule in human intestine and liver, it will be important to: (1) identify interacting proteins which are involved in biosynthesis and/or assembly of CDld using the yeast two-hybrid system, phage display technologies, and biosynthetic labelling; (2) characterize the responses of human intestinal lymphocytes to CDld by measuring proliferation and cytokine production, and (3) identify CDld interacting surface ligand(s) on T-cells using immunoprecipitation with Fc-CDld fusion protein.