Centre for Biologics Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada and WHO Collaborating Center for Standardization and Evaluation of Biologicals, 251 Sir Frederick Banting Driveway, K1A 0K9, Ottawa, ON, Canada; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Roger Guindon Campus, Ottawa, ON, Canada.
Centre for Biologics Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada and WHO Collaborating Center for Standardization and Evaluation of Biologicals, 251 Sir Frederick Banting Driveway, K1A 0K9, Ottawa, ON, Canada.
Biochem Biophys Res Commun. 2018 Jul 12;502(2):226-231. doi: 10.1016/j.bbrc.2018.05.148. Epub 2018 May 24.
Human infections by type B influenza virus constitute about 25% of all influenza cases. The viral hemagglutinin is comprised of two subunits, HA1 and HA2. While HA1 is constantly evolving in an unpredictable fashion, the HA2 subunit is highly conserved, making it a potential candidate for a universal vaccine. However, immunodominant epitopes in the HA2 subunit remain largely unknown. To delineate MHC Class I epitopes, we first identified 9-mer H-2K-restricted CD8 T cell epitopes in the HA2 domain by in silico analyses, followed by evaluating the immunodominance of these peptides in mice challenged with the virus. Of three peptides selected through in silico analysis, the universally conserved peptide, YYSTAASSL (B/HA2-190), possessed the highest predicted binding affinity to MHC Class I and was most effective in inducing IL-2 and TNF-α in mouse splenocytes. Importantly, the peptide demonstrated best capability of stimulating peptide-specific ex-vivo cytotoxicity against target cells. Taken together, this finding would be of value for assessment of cell-mediated immune responses elicited by vaccines based on the highly conserved HA2 stalk domain.
乙型流感病毒感染约占所有流感病例的 25%。病毒血凝素由两个亚基组成，HA1 和 HA2。虽然 HA1 以不可预测的方式不断进化，但 HA2 亚基高度保守，使其成为通用疫苗的潜在候选者。然而，HA2 亚基中的免疫优势表位在很大程度上仍然未知。为了描绘 MHC I 表位，我们首先通过计算机分析鉴定了 HA2 结构域中 9 -mer H-2K 限制性 CD8 T 细胞表位，然后评估了这些肽在感染病毒的小鼠中的免疫优势。在通过计算机分析选择的三个肽中，普遍保守的肽 YYSTAASSL（B/HA2-190）对 MHC I 的预测结合亲和力最高，在诱导小鼠脾细胞中 IL-2 和 TNF-α方面最有效。重要的是，该肽对针对靶细胞的肽特异性体外细胞毒性具有最佳的刺激能力。总之，这一发现对于评估基于高度保守的 HA2 茎结构域的疫苗引起的细胞介导免疫反应具有重要价值。
