PRESENTATION OF PEPTIDE ANTIGENS BY MOUSE CD1 REQUIRES ENDOSOMAL LOCALIZATION AND PROTEIN ANTIGEN-PROCESSING

Mouse CD1(mCD1) molecules have been reported to present two types of a ntigens: peptides or proteins and the glycolipid alpha-galactosylceram ide. Here, we demonstrate that a protein antigen, chicken ovalbumin (O va), must be processed to generate peptides presented by mCD1 to CD8() T cells. The processing and mCD1-mediated presentation of chicken Ov a depend on endosomal localization because inhibitors of endosomal aci dification and endosomal recycling pathways block T cell reactivity, F urthermore, a cytoplasmic tail mutant of mCD1, which disrupts endosoma l localization, has a greatly reduced capacity to present Ova to mCD1 restricted cells. Newly synthesized mCD1 molecules, however, are not r equired 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 exogen ous proteins, we conclude that peptide antigen presentation by mCD1 is likely to be a naturally occurring phenomenon. In competition assays, alpha-galactosylceramide did not inhibit Ova presentation, and presen tation of the glycolipid was not inhibited by excess Ova or the peptid e epitope derived from it. This suggests that, although both lipid and peptide presentation may occur naturally, mCD1 may interact different ly with these two types of antigens.