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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Drug Design
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HLA-A2 Antigen / chemistry
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HLA-A2 Antigen / genetics
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HLA-A2 Antigen / metabolism
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Histocompatibility Antigens Class I / chemistry
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Histocompatibility Antigens Class I / metabolism*
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Humans
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Immunodominant Epitopes / chemistry
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Immunodominant Epitopes / genetics
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In Vitro Techniques
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Influenza A Virus, H5N1 Subtype / genetics
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Influenza A Virus, H5N1 Subtype / immunology
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Ligands
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Models, Molecular
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Molecular Structure
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Multiprotein Complexes
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Oligopeptides / chemistry
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Oligopeptides / metabolism
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Photochemistry
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Spectrometry, Mass, Electrospray Ionization
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T-Lymphocytes, Cytotoxic / immunology
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Ultraviolet Rays
Substances
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HLA-A2 Antigen
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Histocompatibility Antigens Class I
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Immunodominant Epitopes
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Ligands
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Multiprotein Complexes
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Oligopeptides