Identification of immediate early gene products of bovine herpes virus 1 (BHV-1) as dominant antigens recognized by CD8 T cells in immune cattle

• Autores: Hart, Jane; MacHugh, Niall D.; Sheldrake, Tara; Nielsen, Morten; Morrison, W. Ivan
• Año de publicación: 2017
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Bovine Herpes Virus 1; Cattle; Cd8 T Cell; Epitope Prediction; T-Cell Antigens
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

In common with other herpes viruses, bovine herpes virus 1 (BHV-1) induces strong virus-specific CD8 T-cell responses. However, there is a paucity of information on the antigenic specificity of the responding T-cells. The development of a system to generate virus-specific CD8 T-cell lines from BHV-1-immune cattle, employing Theileria-transformed cell lines for antigen presentation, has enabled us to address this issue. Use of this system allowed the study to screen for CD8 T-cell antigens that are efficiently presented on the surface of virus-infected cells. Screening of a panel of 16 candidate viral gene products with CD8 T-cell lines from 3 BHV-1-immune cattle of defined MHC genotypes identified 4 antigens, including 3 immediate early (IE) gene products (ICP4, ICP22 and Circ) and a tegument protein (UL49). Identification of the MHC restriction specificities revealed that the antigens were presented by two or three class I MHC alleles in each animal. Six CD8 T-cell epitopes were identified in the three IE proteins by screening of synthetic peptides. Use of an algorithm (NetMHCpan) that predicts the peptide-binding characteristics of restricting MHC alleles confirmed and, in some cases refined, the identity of the epitopes. Analyses of the epitope specificity of the CD8 T-cell lines showed that a large component of the response is directed against these IE epitopes. The results indicate that these IE gene products are dominant targets of the CD8 T-cell response in BHV-I-immune cattle and hence are prime-candidate antigens for the generation of a subunit vaccine.
Fil: Hart, Jane. University of Edinburgh; Reino Unido
Fil: MacHugh, Niall D.. University of Edinburgh; Reino Unido
Fil: Sheldrake, Tara. University of Edinburgh; Reino Unido
Fil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Universidad Nacional de San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Morrison, W. Ivan. University of Edinburgh; Reino Unido