Reconstruction of a pathway of antigen processing and class II MHC peptide capture

Catherine X Moss, Timothy I Tree, Colin Watts

    Research output: Contribution to journalArticlepeer-review

    27 Citations (Scopus)

    Abstract

    Endocytosed antigens are proteolytically processed and small amounts of peptides captured by class II MHC molecules. The details of antigen proteolysis, peptide capture and how destruction of T-cell epitopes is avoided are incompletely understood. Using the tetanus toxin antigen, we show that the introduction of 3-6 cleavage sites is sufficient to trigger a partially unfolded conformation able to bind to class II MHC molecules. The known locations of T-cell epitopes and protease cleavage sites predict that large domains of processed antigen (8-35 kDa) are captured under these conditions. Remarkably, when antigen is bound to the B-cell antigen receptor (BCR), processing can trigger a concerted 'hand-over' reaction whereby BCR-associated processed antigen is captured by neighbouring class II MHC molecules. Early capture of minimally processed antigen and confinement of the processing and class II MHC loading reaction to the membrane plane may improve the likelihood of T-cell epitope survival in the class II MHC pathway and may help explain the reciprocal relationships observed between B- and T-cell epitopes in many protein antigens and autoantigens.
    Original languageEnglish
    Pages (from-to)2137-47
    Number of pages11
    JournalEMBO Journal
    Volume26
    Issue number8
    DOIs
    Publication statusPublished - 18 Apr 2007

    Keywords

    • Amino Acid Sequence
    • Antigen Presentation
    • Cell Line
    • Chromatography, Gel
    • Enzyme-Linked Immunosorbent Assay
    • Epitopes, T-Lymphocyte
    • Flow Cytometry
    • Histocompatibility Antigens Class II
    • Humans
    • Microscopy, Fluorescence
    • Models, Immunological
    • Molecular Sequence Data
    • Peptides
    • Receptors, Antigen, B-Cell
    • Tetanus Toxin

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