Asparagine deamidation perturbs antigen presentation on class II major histocompatibility complex molecules

Catherine X. Moss, Stephen P. Matthews, Douglas J. Lamont, Colin Watts (Lead / Corresponding author)

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    66 Citations (Scopus)
    64 Downloads (Pure)

    Abstract

    Post-translational protein modifications can be recognized by B and T lymphocytes and can potentially make "self"-proteins appear foreign to the immune system. Such modifications may directly affect major histocompatibility complex-restricted T cell recognition of processed peptides or may perturb the processing events that generate such peptides. Using the tetanus toxin C fragment protein as a test case, we show that spontaneous deamidation of asparagine residues interferes with processing by the enzyme asparagine endopeptidase (AEP) and contributes to diminished antigen presentation. Deamidation inhibits AEP action either directly, when asparagine residues targeted by AEP are modified, or indirectly, when adjacent Asn residues are deamidated. Thus, deamidation of long-lived self-proteins may qualitatively or quantitatively affect the spectrum of self-peptides displayed to T cells and may thereby contribute to the onset or exacerbation of autoimmune disease.

    Original languageEnglish
    Pages (from-to)18498-18503
    Number of pages6
    JournalJournal of Biological Chemistry
    Volume280
    Issue number18
    DOIs
    Publication statusPublished - May 2005

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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