Antigens presented by class I major histocompatibility complex (MHC) molecules for recognition by cytotoxic T lymphocytes consist of 8–10-amino-acid-long cytosolic peptides. It is not known whether posttranslationally modified peptides are also presented by class I MHC molecules in vivo. Many different posttranslational modifications occur on cytoplasmic proteins, including a cytosolic O-β-linked glycosylation of serine and threonine residues with N-acetylglucosamine (GlcNAc). Using synthetic glycopeptides carrying the monosaccharide O-β-GlcNAc substitution on serine residues, we have shown that glycopeptides bind efficiently to class I MHC molecules and elicit a glycopeptide-specific cytotoxic T lymphocyte response in mice. In this study, we provide evidence that peptides presented by human class I MHC molecules in vivo encompass a small, significant amount of glycopeptides, constituting up to 0.1% of total peptide. Furthermore, we find that carbohydrate structures present on glycopeptides isolated from class I MHC molecules are dominated by the cytosolic O-β-GlcNAc substitution, and synthetic peptides carrying this substitution are efficiently transported by TAP (transporter associated with antigen presentation) into the endoplasmic reticulum. Thus, in addition to unmodified peptides, posttranslationally modified cytosolic peptides carrying O-β-linked GlcNAc can be presented by class I MHC molecules to the immune system.
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1 July 1999
Brief Definitive Report|
July 05 1999
Presentation of Cytosolic Glycosylated Peptides by Human Class I Major Histocompatibility Complex Molecules in Vivo
John S. Haurum,
John S. Haurum
aFrom the Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, England
cInstitute of Cancer Biology, Danish Cancer Society, 2100 Copenhagen, Denmark
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Ingelise Bjerring Høier,
Ingelise Bjerring Høier
cInstitute of Cancer Biology, Danish Cancer Society, 2100 Copenhagen, Denmark
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Gemma Arsequell,
Gemma Arsequell
dUnit of Glycoconjugate Chemistry, CID-CSIC, E08034 Barcelona, Spain
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Anne Neisig,
Anne Neisig
eNetherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
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Gregorio Valencia,
Gregorio Valencia
dUnit of Glycoconjugate Chemistry, CID-CSIC, E08034 Barcelona, Spain
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Jesper Zeuthen,
Jesper Zeuthen
cInstitute of Cancer Biology, Danish Cancer Society, 2100 Copenhagen, Denmark
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Jacques Neefjes,
Jacques Neefjes
eNetherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
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Tim Elliott
Tim Elliott
bFrom the Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford OX3 9DU, England
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John S. Haurum
aFrom the Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, England
cInstitute of Cancer Biology, Danish Cancer Society, 2100 Copenhagen, Denmark
Ingelise Bjerring Høier
cInstitute of Cancer Biology, Danish Cancer Society, 2100 Copenhagen, Denmark
Gemma Arsequell
dUnit of Glycoconjugate Chemistry, CID-CSIC, E08034 Barcelona, Spain
Anne Neisig
eNetherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
Gregorio Valencia
dUnit of Glycoconjugate Chemistry, CID-CSIC, E08034 Barcelona, Spain
Jesper Zeuthen
cInstitute of Cancer Biology, Danish Cancer Society, 2100 Copenhagen, Denmark
Jacques Neefjes
eNetherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
Tim Elliott
bFrom the Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford OX3 9DU, England
Received:
December 07 1998
Revision Requested:
April 21 1999
Accepted:
April 22 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 1999 The Rockefeller University Press
1999
The Rockefeller University Press
J Exp Med (1999) 190 (1): 145–150.
Article history
Received:
December 07 1998
Revision Requested:
April 21 1999
Accepted:
April 22 1999
Citation
John S. Haurum, Ingelise Bjerring Høier, Gemma Arsequell, Anne Neisig, Gregorio Valencia, Jesper Zeuthen, Jacques Neefjes, Tim Elliott; Presentation of Cytosolic Glycosylated Peptides by Human Class I Major Histocompatibility Complex Molecules in Vivo. J Exp Med 1 July 1999; 190 (1): 145–150. doi: https://doi.org/10.1084/jem.190.1.145
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