11
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      H7N9 T-cell epitopes that mimic human sequences are less immunogenic and may induce Treg-mediated tolerance

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Related collections

          Most cited references42

          • Record: found
          • Abstract: found
          • Article: not found

          Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus

          New England Journal of Medicine, 368(20), 1888-1897
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Reorganizing the protein space at the Universal Protein Resource (UniProt)

            The mission of UniProt is to support biological research by providing a freely accessible, stable, comprehensive, fully classified, richly and accurately annotated protein sequence knowledgebase, with extensive cross-references and querying interfaces. UniProt is comprised of four major components, each optimized for different uses: the UniProt Archive, the UniProt Knowledgebase, the UniProt Reference Clusters and the UniProt Metagenomic and Environmental Sequence Database. A key development at UniProt is the provision of complete, reference and representative proteomes. UniProt is updated and distributed every 4 weeks and can be accessed online for searches or download at http://www.uniprot.org.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus.

              A new pandemic influenza A (H1N1) virus has emerged, causing illness globally, primarily in younger age groups. To assess the level of preexisting immunity in humans and to evaluate seasonal vaccine strategies, we measured the antibody response to the pandemic virus resulting from previous influenza infection or vaccination in different age groups. Using a microneutralization assay, we measured cross-reactive antibodies to pandemic H1N1 virus (2009 H1N1) in stored serum samples from persons who either donated blood or were vaccinated with recent seasonal or 1976 swine influenza vaccines. A total of 4 of 107 persons (4%) who were born after 1980 had preexisting cross-reactive antibody titers of 40 or more against 2009 H1N1, whereas 39 of 115 persons (34%) born before 1950 had titers of 80 or more. Vaccination with seasonal trivalent inactivated influenza vaccines resulted in an increase in the level of cross-reactive antibody to 2009 H1N1 by a factor of four or more in none of 55 children between the ages of 6 months and 9 years, in 12 to 22% of 231 adults between the ages of 18 and 64 years, and in 5% or less of 113 adults 60 years of age or older. Seasonal vaccines that were formulated with adjuvant did not further enhance cross-reactive antibody responses. Vaccination with the A/New Jersey/1976 swine influenza vaccine substantially boosted cross-reactive antibodies to 2009 H1N1 in adults. Vaccination with recent seasonal nonadjuvanted or adjuvanted influenza vaccines induced little or no cross-reactive antibody response to 2009 H1N1 in any age group. Persons under the age of 30 years had little evidence of cross-reactive antibodies to the pandemic virus. However, a proportion of older adults had preexisting cross-reactive antibodies. 2009 Massachusetts Medical Society
                Bookmark

                Author and article information

                Journal
                Hum Vaccin Immunother
                Hum Vaccin Immunother
                KHVI
                Human Vaccines & Immunotherapeutics
                Taylor & Francis
                2164-5515
                2164-554X
                September 2015
                19 June 2015
                : 11
                : 9
                : 2241-2252
                Affiliations
                [1 ]Institute for Immunology and Informatics; University of Rhode Island ; Providence, RI USA
                [2 ]EpiVax Inc. ; Providence, RI USA
                [3 ]Laboratory of Applied Molecular Biology (LBMA); University of Bamako ; Bamako, Mali
                Author notes
                [* ]Correspondence to: Anne S De Groot; Email: dr.annie.degroot@ 123456gmail.com
                Article
                1052197
                10.1080/21645515.2015.1052197
                4635734
                26090577
                50cb732e-af5c-4cfb-9132-3805f54ae465
                © 2015 The Author(s). Published with license by Taylor & Francis Group, LLC© Rui Liu, Leonard Moise, Ryan Tassone, Andres H Gutierrez, Frances E Terry, Kotou Sangare, Matthew T Ardito, William D Martin, and Anne S De Groot

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.

                History
                : 19 December 2014
                : 28 April 2015
                : 13 May 2015
                Page count
                Figures: 6, Tables: 2, References: 54, Pages: 12
                Categories
                Research Paper

                Molecular medicine
                cross-conservation,h7n9 influenza,immune evasion,immunoinformatics,janusmatrix,regulatory t cells (tregs),tolerance,vaccine

                Comments

                Comment on this article