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Hum Vaccin Immunother. 2015 Jun 19:0. [Epub ahead of print]
H7N9 T-cell epitopes that mimic human sequences are less immunogenic and may induce Treg-mediated tolerance.
Liu R1, Moise L, Tassone R, Gutierrez AH, Terry FE, Sangare K, Ardito MT, Martin WD, De Groot AS.
Author information
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 diminish seroconversion rates that have been observed in human infections and vaccine trials. We found that the magnitude of human T effector responses to individual H7N9 peptides was inversely correlated with degree of 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.
KEYWORDS:
A(H1N1)pdm09, pandemic H1N1; DPBS, Dulbecco's phosphate-buffered saline; EBV, Epstein Barr Virus; ELISpot, enzyme-linked immunospot; H7N9 influenza; H7N9, H7N9 avian influenza; HA, hemagglutinin; HCV, hepatitis C virus; HI, hemagglutination inhibiting; HIV, human immunodeficiency virus; HLA, human leukocyte antigen; HSV, herpes simplex virus; IAV, influenza A virus; ICS, immunogenic consensus sequences; JanusMatrix; LAIV, live attenuated influenza vaccine; NA, neuraminidase; PBMC, peripheral blood mononuclear cells; SI, stimulation index; TCR, T cell receptor; TRF, time resolved fluorescence; Tregs, T regulatory cells; cross-conservation; immune evasion; immunoinformatic; regulatory T cells (Tregs); tolerance; vaccine
PMID: 26090577 [PubMed - as supplied by publisher]
H7N9 T-cell epitopes that mimic human sequences are less immunogenic and may induce Treg-mediated tolerance.
Liu R1, Moise L, Tassone R, Gutierrez AH, Terry FE, Sangare K, Ardito MT, Martin WD, De Groot AS.
Author information
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 diminish seroconversion rates that have been observed in human infections and vaccine trials. We found that the magnitude of human T effector responses to individual H7N9 peptides was inversely correlated with degree of 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.
KEYWORDS:
A(H1N1)pdm09, pandemic H1N1; DPBS, Dulbecco's phosphate-buffered saline; EBV, Epstein Barr Virus; ELISpot, enzyme-linked immunospot; H7N9 influenza; H7N9, H7N9 avian influenza; HA, hemagglutinin; HCV, hepatitis C virus; HI, hemagglutination inhibiting; HIV, human immunodeficiency virus; HLA, human leukocyte antigen; HSV, herpes simplex virus; IAV, influenza A virus; ICS, immunogenic consensus sequences; JanusMatrix; LAIV, live attenuated influenza vaccine; NA, neuraminidase; PBMC, peripheral blood mononuclear cells; SI, stimulation index; TCR, T cell receptor; TRF, time resolved fluorescence; Tregs, T regulatory cells; cross-conservation; immune evasion; immunoinformatic; regulatory T cells (Tregs); tolerance; vaccine
PMID: 26090577 [PubMed - as supplied by publisher]