Cargando…

Presentation of Cytosolic Glycosylated Peptides by Human Class I Major Histocompatibility Complex Molecules in Vivo

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 differ...

Descripción completa

Detalles Bibliográficos
Autores principales: Haurum, John S., Høier, Ingelise Bjerring, Arsequell, Gemma, Neisig, Anne, Valencia, Gregorio, Zeuthen, Jesper, Neefjes, Jacques, Elliott, Tim
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1999
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195561/
https://www.ncbi.nlm.nih.gov/pubmed/10429679
_version_ 1782147873958264832
author Haurum, John S.
Høier, Ingelise Bjerring
Arsequell, Gemma
Neisig, Anne
Valencia, Gregorio
Zeuthen, Jesper
Neefjes, Jacques
Elliott, Tim
author_facet Haurum, John S.
Høier, Ingelise Bjerring
Arsequell, Gemma
Neisig, Anne
Valencia, Gregorio
Zeuthen, Jesper
Neefjes, Jacques
Elliott, Tim
author_sort Haurum, John S.
collection PubMed
description 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.
format Text
id pubmed-2195561
institution National Center for Biotechnology Information
language English
publishDate 1999
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-21955612008-04-22 Presentation of Cytosolic Glycosylated Peptides by Human Class I Major Histocompatibility Complex Molecules in Vivo Haurum, John S. Høier, Ingelise Bjerring Arsequell, Gemma Neisig, Anne Valencia, Gregorio Zeuthen, Jesper Neefjes, Jacques Elliott, Tim J Exp Med Brief Definitive Report 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. The Rockefeller University Press 1999-07-01 /pmc/articles/PMC2195561/ /pubmed/10429679 Text en © 1999 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Brief Definitive Report
Haurum, John S.
Høier, Ingelise Bjerring
Arsequell, Gemma
Neisig, Anne
Valencia, Gregorio
Zeuthen, Jesper
Neefjes, Jacques
Elliott, Tim
Presentation of Cytosolic Glycosylated Peptides by Human Class I Major Histocompatibility Complex Molecules in Vivo
title Presentation of Cytosolic Glycosylated Peptides by Human Class I Major Histocompatibility Complex Molecules in Vivo
title_full Presentation of Cytosolic Glycosylated Peptides by Human Class I Major Histocompatibility Complex Molecules in Vivo
title_fullStr Presentation of Cytosolic Glycosylated Peptides by Human Class I Major Histocompatibility Complex Molecules in Vivo
title_full_unstemmed Presentation of Cytosolic Glycosylated Peptides by Human Class I Major Histocompatibility Complex Molecules in Vivo
title_short Presentation of Cytosolic Glycosylated Peptides by Human Class I Major Histocompatibility Complex Molecules in Vivo
title_sort presentation of cytosolic glycosylated peptides by human class i major histocompatibility complex molecules in vivo
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195561/
https://www.ncbi.nlm.nih.gov/pubmed/10429679
work_keys_str_mv AT haurumjohns presentationofcytosolicglycosylatedpeptidesbyhumanclassimajorhistocompatibilitycomplexmoleculesinvivo
AT høieringelisebjerring presentationofcytosolicglycosylatedpeptidesbyhumanclassimajorhistocompatibilitycomplexmoleculesinvivo
AT arsequellgemma presentationofcytosolicglycosylatedpeptidesbyhumanclassimajorhistocompatibilitycomplexmoleculesinvivo
AT neisiganne presentationofcytosolicglycosylatedpeptidesbyhumanclassimajorhistocompatibilitycomplexmoleculesinvivo
AT valenciagregorio presentationofcytosolicglycosylatedpeptidesbyhumanclassimajorhistocompatibilitycomplexmoleculesinvivo
AT zeuthenjesper presentationofcytosolicglycosylatedpeptidesbyhumanclassimajorhistocompatibilitycomplexmoleculesinvivo
AT neefjesjacques presentationofcytosolicglycosylatedpeptidesbyhumanclassimajorhistocompatibilitycomplexmoleculesinvivo
AT elliotttim presentationofcytosolicglycosylatedpeptidesbyhumanclassimajorhistocompatibilitycomplexmoleculesinvivo