Recognition of carbohydrate by major histocompatibility complex class I- restricted, glycopeptide-specific cytotoxic T lymphocytes

doi:10.1084/jem.180.2.739

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Recognition of carbohydrate by major histocompatibility complex class I- restricted, glycopeptide-specific cytotoxic T lymphocytes

JS Haurum, G Arsequell, AC Lellouch, SY Wong, RA Dwek, AJ McMichael and T Elliott
Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.

Cytotoxic T cells (CTL) recognize short peptide epitopes presented by class I glycoproteins encoded by the major histocompatibility complex (MHC). It is not yet known whether peptides containing posttranslationally modified amino acids can also be recognized by CTL. To address this issue, we have studied the immunogenicity and recognition of a glycopeptide carrying an O-linked N-acetylglucosamine (GlcNAc) monosaccharide-substituted serine residue. This posttranslational modification is catalyzed by a recently described cytosolic glycosyltransferase. We show that glycosylation does not affect peptide binding to MHC class I and that glycopeptides can elicit a strong CTL response that is glycopeptide specific. Furthermore, glycopeptide recognition by cytotoxic T cells is dependent on the chemical structure of the glycan as well as its position within the peptide.
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