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

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 c...

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Detalles Bibliográficos
Autores: Lorente, Elena, Martin-Galiano, Antonio Javier, Barnea, Eilon, Barriga, Alejandro, Palomo-Sanz, Concepcion, García-Arriaza, Juan, Mir-Gerrero, Carmen, Lauzurica, Pilar, Esteban, Mariano, Admon, Arie, Lopez, Daniel
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/17468
Acceso en línea:http://hdl.handle.net/20.500.12105/17468
Access Level:acceso abierto
Palabra clave:Ligands
Viral Structural Proteins
Cells, Cultured
Gene Expression
Histocompatibility Antigens Class II
Humans
Mass Spectrometry
Poxviridae
Proteomics
Vaccinia
Vaccinia virus
Viral Proteins
Viral Vaccines
Virion
Descripción
Sumario: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.