PMID- 21914809 OWN - NLM STAT- MEDLINE DCOM- 20120109 LR - 20220321 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 286 IP - 44 DP - 2011 Nov 4 TI - Allele-dependent processing pathways generate the endogenous human leukocyte antigen (HLA) class I peptide repertoire in transporters associated with antigen processing (TAP)-deficient cells. PG - 38054-38059 LID - S0021-9258(20)50647-9 [pii] LID - 10.1074/jbc.M111.281808 [doi] AB - 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. FAU - Lorente, Elena AU - Lorente E AD - Centro Nacional de Microbiologia, Instituto de Salud Carlos III, 28220 Majadahonda (Madrid), Spain. FAU - Garcia, Ruth AU - Garcia R AD - Centro Nacional de Microbiologia, Instituto de Salud Carlos III, 28220 Majadahonda (Madrid), Spain. FAU - Lopez, Daniel AU - Lopez D AD - Centro Nacional de Microbiologia, Instituto de Salud Carlos III, 28220 Majadahonda (Madrid), Spain. Electronic address: dlopez@isciii.es. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110913 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 2) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Antigens) RN - 0 (HLA Antigens) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Ligands) RN - 0 (Peptides) RN - 0 (Protease Inhibitors) RN - 0 (TAP1 protein, human) RN - EC 3.4.- (Peptide Hydrolases) SB - IM MH - ATP Binding Cassette Transporter, Subfamily B, Member 2 MH - ATP-Binding Cassette Transporters/*metabolism MH - Alleles MH - Antigens/chemistry MH - CD8-Positive T-Lymphocytes/cytology/metabolism MH - Cell Line MH - Cytosol/metabolism MH - Endoplasmic Reticulum/metabolism MH - HLA Antigens/*chemistry MH - Histocompatibility Antigens Class I/*chemistry MH - Humans MH - Ligands MH - Peptide Hydrolases/chemistry MH - Peptides/chemistry MH - Protease Inhibitors/pharmacology MH - Protein Transport MH - Surface Properties PMC - PMC3207402 EDAT- 2011/09/15 06:00 MHDA- 2012/01/10 06:00 PMCR- 2012/11/04 CRDT- 2011/09/15 06:00 PHST- 2011/09/15 06:00 [entrez] PHST- 2011/09/15 06:00 [pubmed] PHST- 2012/01/10 06:00 [medline] PHST- 2012/11/04 00:00 [pmc-release] AID - S0021-9258(20)50647-9 [pii] AID - M111.281808 [pii] AID - 10.1074/jbc.M111.281808 [doi] PST - ppublish SO - J Biol Chem. 2011 Nov 4;286(44):38054-38059. doi: 10.1074/jbc.M111.281808. Epub 2011 Sep 13.