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Peptide Scanning-assisted Identification of a Monoclonal Antibody-recognized Linear B-cell Epitope
08:09

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Single residue within the antigen translocation complex TAP controls the epitope repertoire by stabilizing a

Christoph Baldauf1, Susanne Schrodt, Meike Herget

  • 1Institute of Biochemistry, Center for Membrane Proteomics, and Cluster of Excellence Frankfurt-Macromolecular Complexes, Goethe-University Frankfurt, Max-von-Laue-Strasse 9, D-60438 Frankfurt/Main, Germany.

Proceedings of the National Academy of Sciences of the United States of America
|May 5, 2010
PubMed

The recognition of virus infected or malignantly transformed cells by cytotoxic T lymphocytes critically depends on the transporter associated with antigen processing (TAP), which delivers proteasomal degradation products into the endoplasmic reticulum lumen for subsequent loading of major histocompatibility complex class I molecules. Here we have identified a single cysteinyl residue in the TAP complex that modulates peptide binding and translocation, thereby restricting the epitope repertoire. Cysteine 213 in human TAP2 was found to be part of a newly uncovered substrate-binding site crucial for peptide recognition. This residue contacts the peptide in the binding pocket in an orientated manner. The translocation complex can be reversibly inactivated by thiol modification of this cysteinyl residue. As part of an unexpected mechanism, this residue is crucial in complementing the binding pocket for a given subset of epitopes as well as in maintaining a substrate-receptive conformation of the translocation complex.

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