Vectorial function of major histocompatibility complex class II in a humanintestinal cell line

This study explores the expression and the function of major histocompatibi lity complex class II in the intestinal epithelial cell line CaCo-2, which has been widely used as a model for the human gastrointestinal epithelium. Human leucocyte antigen (HLA)-DR expression on CaCo-2 cells is induceable b y interferon-gamma (IFN-gamma), but responsiveness to IFN-gamma is dependen t on cell differentiation and IFN-gamma availability at the basolateral cel l surface. HLA-DR expression is concentrated in apical cytoplasmic vesicles and on the basolateral cell surface. Invariant chain is expressed in apica l vesicles but is absent from the cell surface. Immunoprecipitation studies show a slow rate of dissociation of HLA-DR from Ii. Double labelling shows some overlap between HLA-DR expression and basolateral endosomal markers b ut no overlap with apical endosomal markers. Functional studies show proces sing and presentation of lysozyme endocytosed from the basolateral, but not apical surfaces. CaCo-2 cells may provide a useful model with which to dis sect the antigen-processing pathways in polarized epithelial cells. The reg ulated access of antigens taken up from the gut lumen to the processing com partments may prevent overloading the immune system with antigens derived f rom normal gut contents.