Proteome-Wide Zika Virus CD4 T Cell Epitope and HLA Restriction Determination

作者：Victoria Campbell, LeAnn P. Nguyen, Elise Snoey, Christopher L. McClurkan, Kerry J. Laing, Lichun Dong, Alessandro Sette, Cecilia S. Lindestam Arlehamn, Danny M Altmann, Rosemary J. Boyton, Justin A. Roby, Michael Gale, Mars Stone, Michael P. Busch, Phillip Norris, David M. Koelle · 发表于：ImmunoHorizons · 年份：2020 · DOI：10.4049/immunohorizons.2000068 · 被引用次数：11 · 研究领域：Mosquito-borne diseases and control、vaccines and immunoinformatics approaches、Virology and Viral Diseases

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 Abs 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 the 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 Ag processing. Sequential query of bulk ZIKV-reactive CD4 T cells with pooled/single ZIKV peptides and molecularly defined 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 a very limited human blood sample availability.