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

Autor:	Campbell VL; Department of Medicine, University of Washington, Seattle, WA 98195., Nguyen L; Department of Medicine, University of Washington, Seattle, WA 98195., Snoey E; Department of Medicine, University of Washington, Seattle, WA 98195., McClurkan CL; Department of Medicine, University of Washington, Seattle, WA 98195., Laing KJ; Department of Medicine, University of Washington, Seattle, WA 98195., Dong L; Department of Medicine, University of Washington, Seattle, WA 98195., Sette A; Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037.; Department of Medicine, University of California-San Diego, La Jolla, CA 92093., Lindestam Arlehamn CS; Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037., Altmann DM; Department of Immunology and Inflammation, Faculty of Medicine, Imperial College London, London SW7 2AZ, United Kingdom., Boyton RJ; Department of Infectious Diseases, Faculty of Medicine, Imperial College London, London SW7 2AZ, United Kingdom., Roby JA; Center for Innate Immunity of Immune Disease, Department of Immunology, University of Washington, Seattle, WA 98109., Gale M Jr; Center for Innate Immunity of Immune Disease, Department of Immunology, University of Washington, Seattle, WA 98109.; Department of Global Health, University of Washington, Seattle, WA 98195.; Department of Microbiology, University of Washington, Seattle, WA 98195., Stone M; Vitalant Research Institute, San Francisco, CA 94118.; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143., Busch MP; Vitalant Research Institute, San Francisco, CA 94118.; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143., Norris PJ; Vitalant Research Institute, San Francisco, CA 94118.; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143., Koelle DM; Department of Medicine, University of Washington, Seattle, WA 98195; dkoelle@medicine.washington.edu.; Department of Global Health, University of Washington, Seattle, WA 98195.; Benaroya Research Institute, Seattle, WA 98101.; Department of Laboratory Medicine, University of Washington, Seattle, WA 98195; and.; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109.
Jazyk:	angličtina
Zdroj:	ImmunoHorizons [Immunohorizons] 2020 Aug 04; Vol. 4 (8), pp. 444-453. Date of Electronic Publication: 2020 Aug 04.
DOI:	10.4049/immunohorizons.2000068
Abstrakt:	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. (Copyright © 2020 The Authors.)
Databáze:	MEDLINE
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