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

Victoria Campbell, LeAnn Nguyen, Elise Snoey, Christopher McClurkan, Kerry Laing, Lichun Dong, Alessandro Sette, Cecilia Lindestram Arlehamn, Danny Altmann, Rosemary Boyton, Justin Roby, Michael Gale Jr, Mars Stone, Michael Busch, Phillip Norris, David Koelle

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
Pages (from-to)444
Number of pages453
JournalImmunoHorizons
Volume4
Issue number8
Publication statusPublished - 04 Aug 2020
Externally publishedYes

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    Campbell, V., Nguyen, L., Snoey, E., McClurkan, C., Laing, K., Dong, L., Sette, A., Lindestram Arlehamn, C., Altmann, D., Boyton, R., Roby, J., Gale Jr, M., Stone, M., Busch, M., Norris, P., & Koelle, D. (2020). Proteome-Wide Zika Virus CD4 T Cell Epitope and HLA Restriction Determination. ImmunoHorizons, 4(8), 444.