To those outside the field of mucosal immunology it must seem incredible that we do not yet understand something so basic as the interaction of protein antigens with the intestinal epithelium. Although we now know in some detail the mechanisms by which the mucosal immune system is regulated and we can construct elegant adjuvant–peptide fusion proteins with systems capable of precise delivery in conjunction with what we think are appropriate cytokines, we know very little of what happens to even the most simple protein antigens during transport. Conversely, the emergence of several good rodent models of intestinal inflammation has had a major impact on our understanding of inflammatory bowel disease pathogenesis, but without further information on T cell–epithelial cell–antigen interactions, the vital mechanisms of the initial “barrier” defect will continue to elude us. Are antigens selectively degraded during transport across the epithelium? If so, is this essential to the maintenance of immune homeostasis? How is the relative transport of intact protein, peptides and amino acids controlled and is the maintenance of a “normal” flora important in this control? All these are vital questions to which we have few sensible responses.

Macromolecular transport by the adult gut epithelium was established in the 1970s, in particular by the extensive work from Allan …