Abstract
HLA-E is an MHC class Ib molecule that binds nonamer peptides derived from the leader sequence of MHC class 1a molecules and is the major ligand for CD94/NKG2 receptors found on NK and T cells. Using the MHC class Ia-null cell line 721.221, we find that surface HLA-E increases following heat shock at 42 degrees C and NK cell-mediated lysis is inhibited using heat-stressed 721.221 targets. We have used mass spectrometry to identify and sequence a novel peptide from HLA-E following heat shock, ALALVRMLI, derived from the transmembrane domain of the human ATP-binding cassette protein, multidrug resistance-associated protein, MRP7. Pulsing 721.221 targets with synthetic MRP7 peptide results in strong inhibition of NK cell-mediated lysis that is reversible using anti-CD94 and anti-class I mAbs. This report is the first to identify a non-MHC leader inhibitory peptide bound to HLA-E and provides insight into the immunoregulatory role of HLA-E during cell stress.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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ATP-Binding Cassette Transporters / metabolism*
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Antigens, CD / metabolism
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Cell Line
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Cytotoxicity Tests, Immunologic
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Cytotoxicity, Immunologic / immunology*
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Epitopes, B-Lymphocyte / biosynthesis
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Epitopes, B-Lymphocyte / metabolism
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Epitopes, B-Lymphocyte / physiology
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HLA Antigens / biosynthesis
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HLA Antigens / metabolism*
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HLA Antigens / physiology
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HLA-E Antigens
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Histocompatibility Antigens Class I / biosynthesis
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Histocompatibility Antigens Class I / metabolism*
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Histocompatibility Antigens Class I / physiology
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Hot Temperature
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Humans
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Immunologic Factors / biosynthesis
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Immunologic Factors / metabolism*
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Immunologic Factors / physiology
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Killer Cells, Natural / immunology*
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Lectins, C-Type / metabolism
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Multidrug Resistance-Associated Proteins / metabolism*
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NK Cell Lectin-Like Receptor Subfamily C
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NK Cell Lectin-Like Receptor Subfamily D
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Osmotic Pressure
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Peptide Fragments / biosynthesis
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Peptide Fragments / metabolism*
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Peptide Fragments / physiology
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Protein Binding / immunology
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Receptors, Immunologic / metabolism
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Receptors, Natural Killer Cell
Substances
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ABCC10 protein, human
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ATP-Binding Cassette Transporters
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Antigens, CD
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Epitopes, B-Lymphocyte
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HLA Antigens
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Histocompatibility Antigens Class I
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Immunologic Factors
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KLRC1 protein, human
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KLRD1 protein, human
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Lectins, C-Type
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Multidrug Resistance-Associated Proteins
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NK Cell Lectin-Like Receptor Subfamily C
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NK Cell Lectin-Like Receptor Subfamily D
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Peptide Fragments
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Receptors, Immunologic
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Receptors, Natural Killer Cell