Presentation of peptide antigens by mouse CD1 requires endosomal localization and protein antigen processing

Abstract

Mouse CD1(mCD1) molecules have been reported to present two types of antigens: peptides or proteins and the glycolipid ␣-galactosylceramide. Here, we demonstrate that a protein antigen, chicken ovalbumin (Ova), must be processed to generate peptides presented by mCD1 to CD8 ؉ T cells. The processing and mCD1-mediated presentation of chicken Ova depend on endosomal localization because inhibitors of endosomal acidification and endosomal recycling pathways block T cell reactivity. Furthermore, a cytoplasmic tail mutant of mCD1, which disrupts endosomal localization, has a greatly reduced capacity to present Ova to mCD1 restricted cells. Newly synthesized mCD1 molecules, however, are not required for Ova presentation, suggesting that molecules recycling from the cell surface are needed. Because of these data showing that mCD1 trafficks to endosomes, where it can bind peptides derived from exogenous proteins, we conclude that peptide antigen presentation by mCD1 is likely to be a naturally occurring phenomenon. In competition assays, ␣-galactosylceramide did not inhibit Ova presentation, and presentation of the glycolipid was not inhibited by excess Ova or the peptide epitope derived from it. This suggests that, although both lipid and peptide presentation may occur naturally, mCD1 may interact differently with these two types of antigens.

Airway Hyperresponsiveness through Synergy of γδ T Cells and NKT Cells

“…However, if such cells are present, they alone are incapable of mediating AHR. Neither the iNKT cells nor the ␥␦ T cells appear to recognize OVA, although it is difficult to rule out this possibility entirely (37,38). Whether they recognize other components in the OVA preparation used for sensitization and challenge (e.g., LPS), autologous ligands induced by the treatment of the recipients, or no ligands at all remains to be determined.…”

Endogenous collagen peptide activation of CD1d-restricted NKT cells ameliorates tissue-specific inflammation in mice

“…How the mCII 707-721 structurally fits into this groove is not clear. Other studies have shown that a CD1d-restricted peptide can elicit a cellular immune response in vivo (17), leading the researchers to opine that intracellular murine CD1d might normally be associated with peptides and therefore peptide presentation may be a true physiologic function of murine CD1d (8).…”

“…An endogenous ligand, isoglobotrihexosylceramide, has been shown to be involved in NKT cell autoreactivity (6). In addition to the association of CD1d with the binding and/or presentation of self and exogenous lipid or glycolipids (6), early reports have also indicated peptidepresenting capacity of CD1d (7)(8)(9).…”

Structure of an α-Helical Peptide and Lipopeptide Bound to the Nonclassical Major Histocompatibility Complex (MHC) Class I Molecule CD1d

“…Later, a peptide from chicken ovalbumin carrying the same motif (p18) was also shown to bind to CD1d and elicit an immune response (13,14). However, even though peptide CD1d-reactive T cells have been reported in these studies, their frequency and role in the context of the immune response remains controversial.…”