The unique surface molecules on intestinal intraepithelial lymphocytes: from tethering to recognizing.

Interspersed among epithelial cells (ECs), intraepithelial lymphocytes (IELs) might be important constituents of the physiological and immunological barriers of the intestinal epithelial layer. IELs are composed of memory-effector T cell subtypes bearing the T cell receptor-γδ (TCRγδ) and TCRαβ. The intimate cell adhesion molecules- and tight junction proteins-mediated biological interactions between IELs and ECs ensure that IELs can reside within the intraepithelial compartment and survey large areas of the villus epithelium. As sentinels in this critical interface, IELs express TCRs that recognize antigenic peptides presented by conventional major histocompatibility complex (MHC) molecules or by non-classical MHC molecules. Moreover, IELs monitor for stressed or damaged ECs to mediate pathological responses and maintain intestinal homeostasis. In this review, we address how IELs reside within the epithelium and exert their sentinel functions.