title: Intramembrane proteolysis of signal peptides: an essential step in the generation of HLA-E epitopes.
abstract: Signal sequences of human MHC class I molecules are a unique source of epitopes for newly synthesized nonclassical HLA-E molecules. Binding of such conserved peptides to HLA-E induces its cell surface expression and protects cells from NK cell attack. After cleavage from the pre-protein, we show that the liberated MHC class I signal peptide is further processed by signal peptide peptidase in the hydrophobic, membrane-spanning region. This cut is essential for the release of the HLA-E epitope-containing fragment from the lipid bilayer and its subsequent transport into the lumen of the endoplasmic reticulum via the TAP.
authors.affiliation: Institute of Biochemistry, Swiss Federal Institute of Technology (Eidgenössiche Technische Hochschule), Zurich, Switzerland.
authors.forename: M K
authors.initials: MK
authors.lastname: Lemberg
authors.forename: F A
authors.initials: FA
authors.lastname: Bland
authors.forename: A
authors.initials: A
authors.lastname: Weihofen
authors.forename: V M
authors.initials: VM
authors.lastname: Braud
authors.forename: B
authors.initials: B
authors.lastname: Martoglio
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000595:Amino Acid Sequence; D002460:Cell Line; D000939:Epitopes / Q000096:biosynthesis* / Q000378:metabolism; D006680:HLA Antigens / Q000096:biosynthesis* / Q000378:metabolism; D015234:HLA-A Antigens / Q000378:metabolism; D015791:HLA-A3 Antigen; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007425:Intracellular Membranes / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000276:immunology; D021382:Protein Sorting Signals; D012697:Serine Endopeptidases / Q000378:metabolism*; D013379:Substrate Specificity / Q000276:immunology; D000097625:HLA-E Antigens
chemical_list: D018528:ATP-Binding Cassette Transporters; D000939:Epitopes; D006680:HLA Antigens; D015234:HLA-A Antigens; D015791:HLA-A3 Antigen; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D010446:Peptide Fragments; D011498:Protein Precursors; D021382:Protein Sorting Signals; D012697:Serine Endopeptidases; D000097625:HLA-E Antigens; C412573:ABCB9 protein, human; C442141:HLA-A*03:01 antigen; C026515:type I signal peptidase