The epithelial cell cytoskeleton and intracellular trafficking. V. Polarized compartmentalization of antigen processing and Toll-like receptor signaling in intestinal epithelial cells.
The intestinal epithelial cell (IEC) is exposed at the apical surface to a high concentration of foreign antigen and bacterial products capable of triggering inflammatory responses. Complex intracellular pathways of antigen trafficking and the polarized expression of immunologically active receptors provide additional means to regulate the inflammatory pathways in these cells. In the case of human leukocyte antigen (HLA) class II heterodimers, surface expression is highly restricted to the basolateral surface, and this also appears to be the case for Toll-like receptor 5 (TLR5) on polarized T84 human colon cancer cells. Processing of soluble antigen via HLA class II in IEC can occur following internalization from the apical surface but is highly inefficient. In addition, certain bacteria can facilitate the transport of flagellin (the ligand for TLR5) across an intact epithelium. Disruption of the tight junctions between IECs, allowing direct access of antigen and flagellin to the basolateral surface of the cell, dramatically affects the functional outcome HLA class II and TLR5 pathways.
Hershberg
Robert M
RM
Corixa Corporation and Infectious Disease Research Institute, Seattle, Washington 98104, USA. hershberg@corixa.com
D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D003110:Colonic Neoplasms / Q000737:chemistry / Q000648:ultrastructure; D019281:Dimerization; D029721:Drosophila Proteins; D005408:Flagellin / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure*; D008562:Membrane Glycoproteins / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction; D019108:Tight Junctions / Q000502:physiology; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors
D029721:Drosophila Proteins; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors; D005408:Flagellin