Chapter 8 - MHC-like Molecules on Mucosal Epithelial Cells

Abstract

MHC class Ib molecules are nonpolymorphic MHC class I-like molecules which fulfill functions divergent from the classisal, MHC class Ia molecules. The human intestine is a unique immunologic compartment, which expresses two of these molecules: the neonatal Fc receptor for IgG (FcRn) and CD1. The FcRn is expressed by adult enterocytes where mRNA, protein, and Fc binding of IgG characteristic of this molecule can be detected. This suggests that the FcRn is functional beyond the neonatal period which has important implications for mucosal immune regulation. Whereas CD1d is expressed by intestinal epithelial cells (IEC) and upregulated by IFNγ, CD1a, b, and c are expressed primarily on mononuclear cells of the lamina propria. CD1d can be recognized in its native form on IECs by peripheral CD8+ T cells. CD8+ T intestinal intraepithelial lymphocyte (IEL) T-cell clones can recognize several members of the CD1 gene family in a transfected LA-A,B negative, B-cell line. The IEC appears to express at least two forms of CD1d, a cell surface and intracellular form. The cell surface form that is likely recognized by peripheral CD8+ T cells is distinct from all previously described class 1 MHC molecules, suggesting that it is transported to the cell surface by a distinct pathway and does not function as a conventional antigen-presenting molecule. This form is expressed independently of β2M, without N-linked carbohydrate side-chain modification. Complex transcriptional processing of CD1d also occurs. Thus, distinct structural isoforms of CD1d are detectable which may function in IEL-mucosal T cell interactions.