Data_Sheet_1_Structural Influence on the Dominance of Virus-Specific CD4 T Cell Epitopes in Zika Virus Infection.PDF

Zika virus (ZIKV) has recently caused explosive outbreaks in Pacific islands, South- and Central America. Like with other flaviviruses, protective immunity is strongly dependent on potently neutralizing antibodies (Abs) directed against the viral envelope protein E. Such Ab formation is promoted by CD4 T cells through direct interaction with B cells that present epitopes derived from E or other structural proteins of the virus. Here, we examined the extent and epitope dominance of CD4 T cell responses to capsid (C) and envelope proteins in Zika patients. All patients developed ZIKV-specific CD4 T cell responses, with substantial contributions of C and E. In both proteins, immunodominant epitopes clustered at sites that are structurally conserved among flaviviruses but have highly variable sequences, suggesting a strong impact of protein structural features on immunodominant CD4 T cell responses. Our data are particularly relevant for designing flavivirus vaccines and their evaluation in T cell assays and provide insights into the importance of viral protein structure for epitope selection and antigenicity.

寨卡病毒（ZIKV）近期在太平洋岛屿、南美和中美洲引发了爆发性疫情。与其他黄病毒类似，保护性免疫高度依赖于针对病毒包膜蛋白E的强效中和抗体（Abs）。此类抗体的形成通过CD4 T细胞与展示由E或其他病毒结构蛋白（如包膜蛋白C）来源的表位的B细胞直接相互作用而得到促进。在本研究中，我们探讨了寨卡病毒患者对包膜蛋白C和E的CD4 T细胞反应的范围和表位优势。所有患者均产生了针对ZIKV的特异性CD4 T细胞反应，其中包膜蛋白C和E做出了重要贡献。在这两种蛋白中，免疫优势表位聚集在黄病毒家族中结构上保守但序列高度可变的位点，这表明蛋白质的结构特征对免疫优势CD4 T细胞反应具有显著影响。我们的数据对于设计黄病毒疫苗及其在T细胞检测中的评估具有重要意义，并揭示了病毒蛋白结构在表位选择和抗原性中的重要性。