Lorente Elena, Barriga Alejandro, Barnea Eilon, Mir Carmen, Gebe John A, Admon Arie, López Daniel
From the ‡Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220 Majadahonda (Madrid), Spain.
§Department of Biology, Technion-Israel Institute of Technology, 32000 Haifa, Israel.
Mol Cell Proteomics. 2016 Jun;15(6):2141-51. doi: 10.1074/mcp.M115.057356. Epub 2016 Apr 18.
Proper antiviral humoral and cellular immune responses require previous recognition of viral antigenic peptides that are bound to HLA class II molecules, which are exposed on the surface of antigen-presenting cells. The helper immune response is critical for the control and the clearance of human respiratory syncytial virus (HRSV) infection, a virus with severe health risk in infected pediatric, immunocompromised, and elderly populations. In this study, using a mass spectrometry analysis of complex HLA class II-bound peptide pools that were isolated from large amounts of HRSV-infected cells, 19 naturally processed HLA-DR ligands, most of them included in a complex nested set of peptides, were identified. Both the immunoprevalence and the immunodominance of the HLA class II response to HRSV were focused on one nonstructural (NS1) and two structural (matrix and mainly fusion) proteins of the infective virus. These findings have clear implications for analysis of the helper immune response as well as for antiviral vaccine design.
适当的抗病毒体液免疫和细胞免疫反应需要预先识别与 HLA II 类分子结合的病毒抗原肽，这些分子暴露于抗原呈递细胞表面。辅助性免疫反应对于控制和清除人呼吸道合胞病毒（HRSV）感染至关重要，该病毒在受感染的儿童、免疫功能低下者和老年人群中具有严重的健康风险。在本研究中，通过对从大量 HRSV 感染细胞中分离出的复杂 HLA II 类结合肽库进行质谱分析，鉴定出了 19 种天然加工的 HLA-DR 配体，其中大多数包含在一组复杂的嵌套肽中。HLA II 类对 HRSV 反应的免疫流行率和免疫优势均集中在感染病毒的一种非结构（NS1）蛋白和两种结构（基质蛋白和主要是融合蛋白）上。这些发现对辅助性免疫反应分析以及抗病毒疫苗设计具有明确的意义。
