Proteome-wide Zika virus CD4 T cell epitope and HLA restriction determination
File(s)
Published version
OA Location
Author(s)
Type
Journal Article
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.
Date Issued
2020-08-01
Date Acceptance
2020-07-13
Citation
ImmunoHorizons, 2020, 4 (8), pp.444-453
ISSN
2573-7732
Publisher
American Association of Immunologists
Start Page
444
End Page
453
Journal / Book Title
ImmunoHorizons
Volume
4
Issue
8
Copyright Statement
© 2020 The Authors. This article is distributed under the terms of theCC BY 4.0 Unported license (https://creativecommons.org/licenses/by/4.0/)
License URL
Sponsor
Medical Research Council (MRC)
Medical Research Council
National Institutes of Health
Innovate UK
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/32753403
PII: 4/8/444
Grant Number
MC_PC_15106
MC_PC_15106
BPO: 20151; UWSC9568
87242-544164
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2020-08-04