Peptide anchor residue glycosylation: effect on class I major histocompatibility complex binding and cytotoxic T lymphocyte recognition

Eur J Immunol. 1995 Dec;25(12):3270-6. doi: 10.1002/eji.1830251211.


This study extends our previous observation that glycopeptides bind to class I major histocompatibility complex (MHC) molecules and elicit carbohydrate-specific CTL responses. The Sendai virus nucleoprotein wild-type (WT) peptide (FAPGNYPAL) binds H-2Db using the P5-Asn as an anchor. The peptide K2 carrying a P5 serine substitution did not bind Db. Surprisingly, glycosylation of the serine (K2-O-GlcNAc) with N-acetylglucosamine (GlcNAc), a novel cytosolic O-linked glycosylation, partially restored peptide binding to Db. We argue that the N-acetyl group of GlcNAc may fulfil the hydrogen bonding requirements of the Db pocket which normally accomodates P5-Asn. Glycosylation of the P5-Asn residue itself abrogated binding similar to K2, probably for steric reasons. The peptide K2-O-GlcNAc readily elicited Db-restricted cytotoxic T lymphocytes (CTL), which did not cross-react with K2 or WT. However, all Db-restricted CTL raised against K2-O-GlcNAc cross-reacted strongly with another glycopeptide, K3-O-GlcNAc, where the GlcNAc substitution is on a neighboring P4-Ser. Furthermore, Db-restricted CTL clones raised against K2-O-GlcNAc or K3-O-GlcNAc displayed a striking TCR conservation. Our interpretation is that the carbohydrate of K2-O-GlcNAc not only mediates binding to Db, but also interacts with the TCR in such a way as to mimic K3-O-GlcNAc. This unusual example of molecular mimicry extends the known effects of peptide glycosylation from what we and others have previously reported: glycosylation may create a T cell neo-epitope, or, conversely, abrogate recognition. Alternatively, glycosylation may block peptide binding to MHC class I and finally, as reported here, restore binding, presumably through direct interaction of the carbohydrate with the MHC molecule.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / chemistry
  • Acetylglucosamine / pharmacology
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cytotoxicity, Immunologic / drug effects
  • Glycopeptides / chemistry
  • Glycopeptides / pharmacology
  • Glycosylation
  • H-2 Antigens / chemistry*
  • H-2 Antigens / pharmacology*
  • Histocompatibility Antigen H-2D
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Peptide Fragments / chemistry*
  • Peptide Fragments / immunology*
  • Peptide Fragments / pharmacology
  • Protein Binding / immunology
  • Receptors, Antigen, T-Cell / chemistry
  • T-Lymphocytes, Cytotoxic / immunology*


  • Glycopeptides
  • H-2 Antigens
  • H-2Kb protein, mouse
  • Histocompatibility Antigen H-2D
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • Acetylglucosamine