HIGHLY POLARIZED HLA CLASS-II ANTIGEN-PROCESSING AND PRESENTATION BY HUMAN INTESTINAL EPITHELIAL-CELLS

The high concentration of foreign antigen in the lumen of the gastroin testinal tract is separated from the underlying lymphocytes by a singl e cell layer of polarized epithelium. Intestinal epithelial cells can express HLA class n. antigens and may function as antigen-presenting c ells to CD4(+) T cells within the intestinal mucosa, Using tetanus tor oid specific and HLA-DR-restricted T lymphocytes, we show that polariz ed intestinal epithelial cells directed to express HLA-DR molecules ar e able to initiate class II processing only after internalization of a ntigen from their apical surface. Coexpression of the class II transac tivator CIITA in these cells, which stimulates highly efficient class II processing without the characteristic decline in barrier function s een in polarized monolayers treated with the proinnammatory cytokine g amma-IFN, facilitates antigen processing from the basolateral surface. In both cases, peptide presentation to T cells via class II molecules was restricted to the basolateral surface. These data indicate a high ly polarized functional architecture for antigen processing and presen tation by intestinal epithelial cells, and suggest that the functional outcome of antigen processing by the intestinal epithelium is both de pendent on the cellular surface at which the foreign antigen is intern alized and by the underlying degree of mucosal inflammation.