Antigen-presenting function of the mouse CD1 molecule.

Abstract

CD1 molecules are distantly related to major histocompatibility complex (MHC)-encoded class I molecules, and they are coexpressed with beta2 microglobulin (beta2m). In the mouse, CD1 is expressed by intestinal epithelial cells and also by some cells in spleen and lymph node. We have shown that surface expression of mouse CD1 (mCD1) is not dependent upon a functional transporter associated with antigen processing (TAP). This, and other data, suggest that mCD1 may acquire peptides in an intracellular compartment other than the endoplasmic reticulum, where classical class I molecules bind peptide. mCD1 molecules also are distinct from classical class I molecules with regard to the types of peptides that they bind. We have demonstrated that mCD1 molecules preferentially bind peptides much longer than the 8-9 amino acids typical of the peptides that bind to classical class I molecules. The sequence motif for mCD1 peptide binding is characterized by the presence of bulky and hydrophobic amino acid side chains. We have generated mCD1-restricted and peptide-specific T-cell lines, thereby demonstrating the immunologic relevance of peptide binding to mCD1. The reactive T cells are TCR alphabeta+ and CD8+, a phenotype typical of many lymphocytes in both lymph node and intestinal mucosae. We speculate that mCD1 molecules may be capable of sampling peptides from the gut lumen and presenting them to mucosal T lymphocytes. In this way, they may function in the maintenance of normal mucosal homeostasis, and perhaps also in the induction of systemic tolerance to antigens delivered by the oral route. In summary, CD1 molecules are a novel category of antigen-presenting molecules that have features in common with class I molecules, features in common with class II, and properties distinct from either subset of antigen-presenting molecules. Further studies of the antigen-presenting function of these molecules are certain to yield new insight into immune regulation and perhaps also into the mechanism of oral tolerance.