PMID- 22298786 OWN - NLM STAT- MEDLINE DCOM- 20120516 LR - 20240406 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 287 IP - 13 DP - 2012 Mar 23 TI - Role of metalloproteases in vaccinia virus epitope processing for transporter associated with antigen processing (TAP)-independent human leukocyte antigen (HLA)-B7 class I antigen presentation. PG - 9990-10000 LID - S0021-9258(20)65412-6 [pii] LID - 10.1074/jbc.M111.314856 [doi] AB - The transporter associated with antigen processing (TAP) translocates the viral proteolytic peptides generated by the proteasome and other proteases in the cytosol to the endoplasmic reticulum lumen. There, they complex with nascent human leukocyte antigen (HLA) class I molecules, which are subsequently recognized by the CD8(+) lymphocyte cellular response. However, individuals with nonfunctional TAP complexes or tumor or infected cells with blocked TAP molecules are able to present HLA class I ligands generated by TAP-independent processing pathways. Herein, using a TAP-independent polyclonal vaccinia virus-polyspecific CD8(+) T cell line, two conserved vaccinia-derived TAP-independent HLA-B*0702 epitopes were identified. The presentation of these epitopes in normal cells occurs via complex antigen-processing pathways involving the proteasome and/or different subsets of metalloproteinases (amino-, carboxy-, and endoproteases), which were blocked in infected cells with specific chemical inhibitors. These data support the hypothesis that the abundant cellular proteolytic systems contribute to the supply of peptides recognized by the antiviral cellular immune response, thereby facilitating immunosurveillance. These data may explain why TAP-deficient individuals live normal life spans without any increased susceptibility to viral infections. FAU - Lorente, Elena AU - Lorente E AD - Instituto de Salud Carlos III, Centro Nacional de Microbiologia, 28220 Majadahonda (Madrid), Spain and. FAU - Garcia, Ruth AU - Garcia R AD - Instituto de Salud Carlos III, Centro Nacional de Microbiologia, 28220 Majadahonda (Madrid), Spain and. FAU - Mir, Carmen AU - Mir C AD - Instituto de Salud Carlos III, Centro Nacional de Microbiologia, 28220 Majadahonda (Madrid), Spain and. FAU - Barriga, Alejandro AU - Barriga A AD - Instituto de Salud Carlos III, Centro Nacional de Microbiologia, 28220 Majadahonda (Madrid), Spain and. FAU - Lemonnier, Francois A AU - Lemonnier FA AD - Unite d'Immunite Cellulaire Antivirale, Departement d'Immunologie, Institut Pasteur, Paris Cedex 15, France. FAU - Ramos, Manuel AU - Ramos M AD - Instituto de Salud Carlos III, Centro Nacional de Microbiologia, 28220 Majadahonda (Madrid), Spain and. FAU - Lopez, Daniel AU - Lopez D AD - Instituto de Salud Carlos III, Centro Nacional de Microbiologia, 28220 Majadahonda (Madrid), Spain and. Electronic address: dlopez@isciii.es. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120201 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Antigens, Ly) RN - 0 (Epitopes) RN - 0 (HLA-B7 Antigen) RN - 0 (Ly6a protein, mouse) RN - 0 (Membrane Proteins) RN - EC 3.4.- (Metalloproteases) RN - EC 3.4.25.1 (Proteasome Endopeptidase Complex) SB - IM CIN - J Biol Chem. 2012 Aug 3;287(32):27047; author reply 27048. PMID: 22865894 MH - Animals MH - *Antigen Presentation MH - Antigens, Ly/genetics/*immunology MH - CD8-Positive T-Lymphocytes/*immunology/metabolism MH - Epitopes/genetics/*immunology MH - HLA-B7 Antigen/genetics/*immunology MH - Humans MH - Membrane Proteins/genetics/*immunology MH - Metalloproteases/genetics/*immunology/metabolism MH - Mice MH - Mice, Transgenic MH - Proteasome Endopeptidase Complex/genetics/immunology MH - Vaccinia/genetics/*immunology MH - Vaccinia virus/genetics/*immunology PMC - PMC3323003 EDAT- 2012/02/03 06:00 MHDA- 2012/05/17 06:00 PMCR- 2013/03/23 CRDT- 2012/02/03 06:00 PHST- 2012/02/03 06:00 [entrez] PHST- 2012/02/03 06:00 [pubmed] PHST- 2012/05/17 06:00 [medline] PHST- 2013/03/23 00:00 [pmc-release] AID - S0021-9258(20)65412-6 [pii] AID - M111.314856 [pii] AID - 10.1074/jbc.M111.314856 [doi] PST - ppublish SO - J Biol Chem. 2012 Mar 23;287(13):9990-10000. doi: 10.1074/jbc.M111.314856. Epub 2012 Feb 1.