Abstract
Major histocompatibility complex (MHC) class I molecules associate with a variety of peptide ligands during biosynthesis and present these ligands on the cell surface for recognition by cytotoxic T cells. We have designed conditional MHC ligands that form stable complexes with MHC molecules but degrade on command, by exposure to a defined photostimulus. 'Empty MHC molecules' generated in this manner can be loaded with arrays of peptide ligands to determine MHC binding properties and to monitor antigen-specific T-cell responses in a high-throughput manner. We document the value of this approach by identifying cytotoxic T-cell epitopes within the H5N1 influenza A/Vietnam/1194/04 genome.
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Acknowledgements
We would like to thank V. Cerundolo (Weatherall Institute of Molecular Medicine) for the A2Kb expression construct and F. Lemonnier (Institut Pasteur) for HLA-A2.1-transgenic mice. We would like to thank A. Pfauth and F. van Diepen for flow cytometry assistance, I. Blonk for help in generation of H5N1 DNA vaccines and H. Hilkmann for peptide synthesis. This work was funded by Netherlands Organization for Scientific Research (NWO) Pioneer (to T.S.) and Vidi (to H.O.) grants.
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The technology described in this manuscript is the subject of a patent application. Based on Netherlands Cancer Institute policy on management of intellectual property, Mireille Toebes, Huib Ovaa and Ton N. M. Schumacher would be entitled to a portion of received royalty income in case of future licensing.
Supplementary information
Supplementary Fig. 1
Conditional ligands for 2.1 and H-2Db. (PDF 739 kb)
Supplementary Fig. 2
Conditional peptide-MHC complexes are sensitive to UV light. (PDF 621 kb)
Supplementary Fig. 3
Sensitivity and specificity of MHC exchange tetramers. (PDF 925 kb)
Supplementary Fig. 4
Detection of antigen-specific T cells with MHC-immunoglobulin dimers and MHC tetramers. (PDF 3140 kb)
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Toebes, M., Coccoris, M., Bins, A. et al. Design and use of conditional MHC class I ligands. Nat Med 12, 246–251 (2006). https://doi.org/10.1038/nm1360
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DOI: https://doi.org/10.1038/nm1360
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