Cutting edge: HLA-E binds a peptide derived from the ATP-binding cassette transporter multidrug resistance-associated protein 7 and inhibits NK cell-mediated lysis.
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.
Wooden
Stacey L
SL
Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Kalb
Suzanne R
SR
Cotter
Robert J
RJ
Soloski
Mark J
MJ
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D015703:Antigens, CD / Q000378:metabolism; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D006680:HLA Antigens / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D006358:Hot Temperature; D006801:Humans; D007155:Immunologic Factors / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D009997:Osmotic Pressure; D010446:Peptide Fragments / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding / Q000276:immunology; D011971:Receptors, Immunologic / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D000097625:HLA-E Antigens
D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; D018985:Epitopes, B-Lymphocyte; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D007155:Immunologic Factors; D037181:Lectins, C-Type; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D010446:Peptide Fragments; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D000097625:HLA-E Antigens; C421142:ABCC10 protein, human; C527054:KLRC1 protein, human; C497869:KLRD1 protein, human