In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 9 ( 2021-9-16), p. e1009842-
Kurzfassung:
The aim of this study was to define the breadth and specificity of dominant SARS-CoV-2-specific T cell epitopes using a comprehensive set of 135 overlapping 15-mer peptides covering the SARS-CoV-2 envelope (E), membrane (M) and nucleoprotein (N) in a cohort of 34 individuals with acute (n = 10) and resolved (n = 24) COVID-19. Following short-term virus-specific in vitro cultivation, the single peptide-specific CD4+ T cell response of each patient was screened using enzyme linked immuno spot assay (ELISpot) and confirmed by single-peptide intracellular cytokine staining (ICS) for interferon-γ (IFN-γ) production. 97% (n = 33) of patients elicited one or more N, M or E-specific CD4+ T cell responses and each patient targeted on average 21.7 (range 0–79) peptide specificities. Overall, we identified 10 N, M or E-specific peptides that showed a response frequency of more than 36% and five of them showed high binding affinity to multiple HLA class II binders in subsequent in vitro HLA binding assays. Three peptides elicited CD4+ T cell responses in more than 55% of all patients, namely Mem_P30 (aa146-160), Mem_P36 (aa176-190), both located within the M protein, and Ncl_P18 (aa86-100) located within the N protein. These peptides were further defined in terms of length and HLA restriction. Based on this epitope and restriction data we developed a novel DRB*11 tetramer (Mem_aa145-164) and examined the ex vivo phenotype of SARS-CoV-2-specific CD4+ T cells in one patient. This detailed characterization of single T cell peptide responses demonstrates that SARS-CoV-2 infection universally primes a broad T cell response directed against multiple specificities located within the N, M and E structural protein.
Materialart:
Online-Ressource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009842
DOI:
10.1371/journal.ppat.1009842.g001
DOI:
10.1371/journal.ppat.1009842.g002
DOI:
10.1371/journal.ppat.1009842.g003
DOI:
10.1371/journal.ppat.1009842.g004
DOI:
10.1371/journal.ppat.1009842.g005
DOI:
10.1371/journal.ppat.1009842.g006
DOI:
10.1371/journal.ppat.1009842.t001
DOI:
10.1371/journal.ppat.1009842.t002
DOI:
10.1371/journal.ppat.1009842.t003
DOI:
10.1371/journal.ppat.1009842.t004
DOI:
10.1371/journal.ppat.1009842.t005
DOI:
10.1371/journal.ppat.1009842.t006
DOI:
10.1371/journal.ppat.1009842.t007
DOI:
10.1371/journal.ppat.1009842.s001
DOI:
10.1371/journal.ppat.1009842.s002
DOI:
10.1371/journal.ppat.1009842.s003
DOI:
10.1371/journal.ppat.1009842.s004
DOI:
10.1371/journal.ppat.1009842.s005
DOI:
10.1371/journal.ppat.1009842.s006
DOI:
10.1371/journal.ppat.1009842.s007
DOI:
10.1371/journal.ppat.1009842.s008
DOI:
10.1371/journal.ppat.1009842.s009
DOI:
10.1371/journal.ppat.1009842.s010
DOI:
10.1371/journal.ppat.1009842.s011
DOI:
10.1371/journal.ppat.1009842.s012
DOI:
10.1371/journal.ppat.1009842.s013
DOI:
10.1371/journal.ppat.1009842.s014
DOI:
10.1371/journal.ppat.1009842.s015
DOI:
10.1371/journal.ppat.1009842.s016
DOI:
10.1371/journal.ppat.1009842.r001
DOI:
10.1371/journal.ppat.1009842.r002
DOI:
10.1371/journal.ppat.1009842.r003
DOI:
10.1371/journal.ppat.1009842.r004
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2021
ZDB Id:
2205412-1
