title: Allele-dependent processing pathways generate the endogenous human leukocyte antigen (HLA) class I peptide repertoire in transporters associated with antigen processing (TAP)-deficient cells.
abstract: The transporters associated with antigen processing (TAP) allow the supply of peptides derived from the cytosol to translocate to the endoplasmic reticulum, where they complex with nascent human leukocyte antigen (HLA) class I molecules. However, infected and tumor cells with TAP molecules blocked or individuals with nonfunctional TAP complexes are able to present HLA class I ligands generated by TAP-independent processing pathways. These peptides are detected by the CD8(+) lymphocyte cellular response. Here, the generation of the overall peptide repertoire associated with four different HLA class I molecules in TAP-deficient cells was studied. Using different protease inhibitors, four different proteolytic specificities were identified. These data demonstrate the different allele-dependent complex processing pathways involved in the generation of the HLA class I peptide repertoire in TAP-deficient cells.
authors.affiliation: Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220 Majadahonda (Madrid), Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Lorente
authors.affiliation: Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220 Majadahonda (Madrid), Spain.
authors.forename: Ruth
authors.initials: R
authors.lastname: García
authors.affiliation: Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220 Majadahonda (Madrid), Spain. Electronic address: dlopez@isciii.es.
authors.forename: Daniel
authors.initials: D
authors.lastname: López
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000483:Alleles; D000941:Antigens / Q000737:chemistry; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006680:HLA Antigens / Q000737:chemistry*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D010447:Peptide Hydrolases / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D011480:Protease Inhibitors / Q000494:pharmacology; D021381:Protein Transport; D013499:Surface Properties
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000941:Antigens; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D010455:Peptides; D011480:Protease Inhibitors; C073119:TAP1 protein, human; D010447:Peptide Hydrolases