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 antigens: peptides or proteins and the glycolipid alpha-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, alpha-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.
Tangri
S
S
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
Brossay
L
L
Burdin
N
N
Lee
D J
DJ
Corr
M
M
Kronenberg
M
M
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D018949:Antigens, CD1 / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002645:Chickens; D003433:Crosses, Genetic; D011992:Endosomes / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000941:Antigens; D018949:Antigens, CD1; D000939:Epitopes; D010446:Peptide Fragments; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; D010047:Ovalbumin