Sun Baozeng, Zhang Junqi, Wang Jiawei, Liu Yang, Sun Hao, Lu Zhenhua, Chen Longyu, Ding Xushen, Pan Jingyu, Hu Chenchen, Yang Shuya, Jiang Dongbo, Yang Kun
Department of Immunology, Basic Medicine School, Air-Force Medical University (the Fourth Military Medical University), Xi'an 710032, China.
Shaanxi Provincial Center for Disease Control and Prevention, Xi'an 710054, China.
Vaccines (Basel). 2022 Apr 6;10(4):564. doi: 10.3390/vaccines10040564.
MHC-I antigen processes and presentation trigger host-specific anti-viral cellular responses during infection, in which epitope-recognizing cytotoxic T lymphocytes eliminate infected cells and contribute to viral clearance through a cytolytic killing effect. In this study, Hantaan virus (HTNV) GP-derived 9-mer dominant epitopes were obtained with high affinity to major HLA-I and H-2 superfamilies. Further immunogenicity and conservation analyses selected 11 promising candidates, and molecule docking (MD) was then simulated with the corresponding MHC-I alleles. Two-way hierarchical clustering revealed the interactions between GP peptides and MHC-I haplotypes. Briefly, epitope hotspots sharing good affinity to a wide spectrum of MHC-I molecules highlighted the biomedical practice for vaccination, and haplotype clusters represented the similarities among individuals during T-cell response establishment. Cross-validation proved the patterns observed through both MD simulation and public data integration. Lastly, 148 HTNV variants yielded six types of major amino acid residue replacements involving four in nine hotspots, which minimally influenced the general potential of MHC-I superfamily presentation. Altogether, our work comprehensively evaluates the pan-MHC-I immunoreactivity of HTNV GP through a state-of-the-art workflow in light of comparative immunology, acknowledges present discoveries, and offers guidance for ongoing HTNV vaccine pursuit.
MHC-I抗原加工与呈递在感染期间触发宿主特异性抗病毒细胞反应,其中识别表位的细胞毒性T淋巴细胞消除受感染细胞,并通过溶细胞杀伤作用促进病毒清除。在本研究中,获得了对主要HLA-I和H-2超家族具有高亲和力的汉坦病毒(HTNV)糖蛋白(GP)衍生的9聚体显性表位。进一步的免疫原性和保守性分析筛选出11个有前景的候选表位,然后用相应的MHC-I等位基因进行分子对接(MD)模拟。双向层次聚类揭示了GP肽与MHC-I单倍型之间的相互作用。简而言之,对广泛的MHC-I分子具有良好亲和力的表位热点突出了疫苗接种的生物医学实践,单倍型簇代表了T细胞反应建立过程中个体之间的相似性。交叉验证证实了通过MD模拟和公共数据整合观察到的模式。最后,148个HTNV变体产生了六种主要氨基酸残基替换类型,涉及九个热点中的四个,这对MHC-I超家族呈递的总体潜力影响最小。总之,我们的工作根据比较免疫学,通过先进的工作流程全面评估了HTNV GP的泛MHC-I免疫反应性,认可了当前的发现,并为正在进行的HTNV疫苗研发提供了指导。