title: H7N9 T-cell epitopes that mimic human sequences are less immunogenic and may induce Treg-mediated tolerance.
abstract: Avian-origin H7N9 influenza is a novel influenza A virus (IAV) that emerged in humans in China in 2013. Using immunoinformatics tools, we identified several H7N9 T cell epitopes with T cell receptor (TCR)-facing residues identical to those of multiple epitopes from human proteins. We hypothesized that host tolerance to these peptides may impair T helper response and contribute to the low titer, weak hemagglutination inhibiting (HI) antibody responses and diminished seroconversion rates that have been observed in human H7N9 infections and vaccine trials. We found that the magnitude of human T effector responses to individual H7N9 peptides was inversely correlated with the peptide's resemblance to self. Furthermore, a promiscuous T cell epitope from the hemagglutinin (HA) protein suppressed responses to other H7N9 peptides when co-administered in vitro. Along with other highly 'human-like' peptides from H7N9, this peptide was also shown to expand FoxP3(+) regulatory T cells (Tregs). Thus, H7N9 may be camouflaged from effective human immune response by T cell epitope sequences that avert or regulate effector T cell responses through host tolerance.
authors.affiliation: a Institute for Immunology and Informatics; University of Rhode Island ; Providence , RI USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.forename: Leonard
authors.initials: L
authors.lastname: Moise
authors.forename: Ryan
authors.initials: R
authors.lastname: Tassone
authors.forename: Andres H
authors.initials: AH
authors.lastname: Gutierrez
authors.forename: Frances E
authors.initials: FE
authors.lastname: Terry
authors.forename: Kotou
authors.initials: K
authors.lastname: Sangare
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Ardito
authors.forename: William D
authors.initials: WD
authors.lastname: Martin
authors.forename: Anne S
authors.initials: AS
authors.lastname: De Groot
mesh_terms: D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D064766:Influenza A Virus, H7N9 Subtype / Q000235:genetics / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte
keywords: H7N9 influenza; JanusMatrix; cross-conservation; immune evasion; immunoinformatics; regulatory T cells (Tregs); tolerance; vaccine