S. Tangri et al., PRESENTATION OF PEPTIDE ANTIGENS BY MOUSE CD1 REQUIRES ENDOSOMAL LOCALIZATION AND PROTEIN ANTIGEN-PROCESSING, Proceedings of the National Academy of Sciences of the United Statesof America, 95(24), 1998, pp. 14314-14319
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.