Proteome-Wide Zika Virus CD4 T Cell Epitope and HLA Restriction Determination.
Proteome-Wide Zika Virus CD4 T Cell Epitope and HLA Restriction Determination.
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DOI：
10.4049/immunohorizons.2000068
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发表时间：
2020-08-04
期刊：
影响因子：
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通讯作者：
Koelle DM
中科院分区：
文献类型：
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作者：
Campbell VL;Nguyen L;Snoey E;McClurkan CL;Laing KJ;Dong L;Sette A;Lindestam Arlehamn CS;Altmann DM;Boyton RJ;Roby JA;Gale M Jr;Stone M;Busch MP;Norris PJ;Koelle DM
寨卡病毒（ZIKV）是一种蚊子传播的病原体，在2015-2016年引起流行。ZIKV特异性T细胞应答在动物感染模型中是功能性的，并且辅助CD 4 T细胞在疫苗背景下促进亲合力抗体。来自现场研究的少量血液限制了复杂微生物如ZIKV的T细胞表位的确定。该项目的目标是在全蛋白质组规模下有效测定人ZIKV CD 4 T细胞表位，包括使用来自T细胞应答幅度可能已经减弱的恢复期时间点的小血液样品验证对全病原体的反应性。候选ZIKV特异性CD 4 T细胞的多克隆富集使用细胞相关病毒，证明下游肽分析中的T细胞也识别抗原加工后的全病毒。用合并的/单一ZIKV肽和分子定义的抗原呈递细胞（APC）对大量ZIKV反应性CD 4 T细胞的顺序查询允许在ZIKV蛋白质组中进行精确的表位和HLA限制性分配，并且能够发现许多新的ZIKV CD 4 T细胞表位。研究工作流程对于研究血液样本非常有限的新发传染病非常有用。
Zika virus (ZIKV) is a mosquito-borne pathogen that caused an epidemic in 2015–2016. ZIKV-specific T cell responses are functional in animal infection models, and helper CD4 T cells promote avid antibodies in the vaccine context. The small volumes of blood available from field research limit the determination of T cell epitopes for complex microbes such as ZIKV. The goal of this project was efficient determination of human ZIKV CD4 T cell epitopes at whole proteome scale, including validation of reactivity to whole pathogen, using small blood samples from convalescent time points when T cell response magnitude may have waned. Polyclonal enrichment of candidate ZIKV-specific CD4 T cells used cell-associated virus, documenting that T cells in downstream peptide analyses also recognize whole virus after antigen processing. Sequential query of bulk ZIKV-reactive CD4 T cells with pooled/single ZIKV peptides and molecularly defined antigen presenting cells (APC) allowed precision epitope and HLA restriction assignments across the ZIKV proteome and enabled discovery of numerous novel ZIKV CD4 T cell epitopes. The research workflow is useful for the study of emerging infectious diseases with very limited blood sample availability.