Modulation of antigen trafficking to MHC class II-positive late endosomes of enterocytes

Background & Aims: Oral tolerance is recognized as a central immunoregulato ry phenomenon. The mechanisms of its induction remain unclear, and the role of the intestinal epithelial cells that are able to present antigens to T lymphocytes is poorly understood. In this report, we analyze under in vivo conditions the intracellular targeting of mucosally administered ovalbumin (OVA) to major histocompatibility complex (MHC) class II antigen containing compartments of enterocytes and compare these pathways between BALB/c and SCID mice, the latter being unable to generate a transferable tolerogenic m oiety after a feed of OVA. Methods: OVA, lysosome-associated membrane prote ins (LAMP-1), and MHC class II antigens were localized in jejunal biopsy sp ecimens of BALB/c and SCID mice at 0, 5, 10, 20, 40, 60, and 120 minutes af ter a single feed with OVA by fluorescence and electron microscopy. Results : Ten minutes after oral administration, OVA was transported to the proximi ty of MHC class II antigens within LAMP-1-positive vacuoles and to the baso lateral membrane of enterocytes from BALB/c strain mice. However, in SCID m ice, OVA reached the paracellular spaces during the same time period throug h LAMP-1-negative vacuoles of enterocytes, which lacked MHC class II antige ns. Conclusions: Orally administered OVA is rapidly targeted to late endoso mes containing LAMP-1 and MHC class II antigens in enterocytes of BALB/c mi ce but not in SCID mice bred on a BALB/c background. We suggest that this t argeting process within the enterocytes is one of the requirements for the induction of oral tolerance.