PMID- 30629447 OWN - NLM STAT- MEDLINE DCOM- 20200528 LR - 20200528 IS - 1535-3907 (Electronic) IS - 1535-3893 (Linking) VI - 18 IP - 3 DP - 2019 Mar 1 TI - Proteomics Analysis Reveals That Structural Proteins of the Virion Core and Involved in Gene Expression Are the Main Source for HLA Class II Ligands in Vaccinia Virus-Infected Cells. PG - 900-911 LID - 10.1021/acs.jproteome.8b00595 [doi] AB - Protective cellular and humoral immune responses require previous recognition of viral antigenic peptides complexed with human leukocyte antigen (HLA) class II molecules on the surface of the antigen presenting cells. The HLA class II-restricted immune response is important for the control and the clearance of poxvirus infection including vaccinia virus (VACV), the vaccine used in the worldwide eradication of smallpox. In this study, a mass spectrometry analysis was used to identify VACV ligands bound to HLA-DR and -DP class II molecules present on the surface of VACV-infected cells. Twenty-six naturally processed viral ligands among the tens of thousands of cell peptides bound to HLA class II proteins were identified. These viral ligands arose from 19 parental VACV proteins: A4, A5, A18, A35, A38, B5, B13, D1, D5, D7, D12, D13, E3, E8, H5, I2, I3, J2, and K2. The majority of these VACV proteins yielded one HLA ligand and were generated mainly, but not exclusively, by the classical HLA class II antigen processing pathway. Medium-sized and abundant proteins from the virion core and/or involved in the viral gene expression were the major source of VACV ligands bound to HLA-DR and -DP class II molecules. These findings will help to understand the effectiveness of current poxvirus-based vaccines and will be important in the design of new ones. FAU - Lorente, Elena AU - Lorente E FAU - Martin-Galiano, Antonio J AU - Martin-Galiano AJ FAU - Barnea, Eilon AU - Barnea E AD - Department of Biology , Technion-Israel Institute of Technology , 32000 Haifa , Israel. FAU - Barriga, Alejandro AU - Barriga A FAU - Palomo, Concepcion AU - Palomo C FAU - Garcia-Arriaza, Juan AU - Garcia-Arriaza J AD - Department of Molecular and Cellular Biology , Centro Nacional de Biotecnologia , Consejo Superior de Investigaciones Cientificas (CSIC), 28049 Madrid , Spain. FAU - Mir, Carmen AU - Mir C FAU - Lauzurica, Pilar AU - Lauzurica P FAU - Esteban, Mariano AU - Esteban M AD - Department of Molecular and Cellular Biology , Centro Nacional de Biotecnologia , Consejo Superior de Investigaciones Cientificas (CSIC), 28049 Madrid , Spain. FAU - Admon, Arie AU - Admon A AD - Department of Biology , Technion-Israel Institute of Technology , 32000 Haifa , Israel. FAU - Lopez, Daniel AU - Lopez D AUID- ORCID: 0000-0003-0268-5878 LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190122 PL - United States TA - J Proteome Res JT - Journal of proteome research JID - 101128775 RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Ligands) RN - 0 (Viral Proteins) RN - 0 (Viral Structural Proteins) RN - 0 (Viral Vaccines) SB - IM MH - Cells, Cultured MH - Gene Expression MH - Histocompatibility Antigens Class II/*metabolism MH - Humans MH - *Ligands MH - Mass Spectrometry MH - Poxviridae/immunology MH - Proteomics/*methods MH - Vaccinia/immunology MH - Vaccinia virus/*chemistry MH - Viral Proteins/immunology MH - *Viral Structural Proteins/immunology MH - Viral Vaccines MH - Virion/*chemistry OTO - NOTNLM OT - HLA OT - T cells OT - antigen processing OT - bioinformatics tools OT - cellular immune response OT - immunoproteomics OT - mass spectrometry OT - peptides OT - vaccine OT - virus EDAT- 2019/01/11 06:00 MHDA- 2020/05/29 06:00 CRDT- 2019/01/11 06:00 PHST- 2019/01/11 06:00 [pubmed] PHST- 2020/05/29 06:00 [medline] PHST- 2019/01/11 06:00 [entrez] AID - 10.1021/acs.jproteome.8b00595 [doi] PST - ppublish SO - J Proteome Res. 2019 Mar 1;18(3):900-911. doi: 10.1021/acs.jproteome.8b00595. Epub 2019 Jan 22.