title: Human immune responses to H. pylori HLA Class II epitopes identified by immunoinformatic methods.
abstract: H. pylori persists in the human stomach over decades and promotes several adverse clinical sequelae including gastritis, peptic ulcers and gastric cancer that are linked to the induction and subsequent evasion of chronic gastric inflammation. Emerging evidence indicates that H. pylori infection may also protect against asthma and some other immune-mediated conditions through regulatory T cell effects outside the stomach. To characterize the complexity of the CD4+ T cell response generated during H. pylori infection, computational methods were previously used to generate a panel of 90 predicted epitopes conserved among H. pylori genomes that broadly cover HLA Class II diversity for maximum population coverage. Here, these sequences were tested individually for their ability to induce in vitro responses in peripheral blood mononuclear cells by interferon-γ ELISpot assay. The average number of spot-forming cells/million PBMCs was significantly elevated in H. pylori-infected subjects over uninfected persons. Ten of the 90 peptides stimulated IFN-γ secretion in the H. pylori-infected group only, whereas two out of the 90 peptides elicited a detectable IFN-γ response in the H. pylori-uninfected subjects but no response in the H. pylori-infected group. Cytokine ELISA measurements performed using in vitro PBMC culture supernatants demonstrated significantly higher levels of TNF-α, IL-2, IL-4, IL-6, IL-10, and TGF-β1 in the H. pylori-infected subjects, whereas IL-17A expression was not related to the subjects H. pylori-infection status. Our results indicate that the human T cell responses to these 90 peptides are generally increased in actively H. pylori-infected, compared with H. pylori-naïve, subjects. This information will improve understanding of the complex immune response to H. pylori, aiding rational epitope-driven vaccine design as well as helping identify other H. pylori epitopes with potentially immunoregulatory effects.
authors.affiliation: Division of Gastroenterology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island, United States of America.
authors.forename: Songhua
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Institute for Immunology and Informatics, University of Rhode Island, Providence, Rhode Island, United States of America.
authors.forename: Joseph
authors.initials: J
authors.lastname: Desrosiers
authors.affiliation: Division of Gastroenterology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island, United States of America.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Aponte-Pieras
authors.affiliation: Institute for Immunology and Informatics, University of Rhode Island, Providence, Rhode Island, United States of America.
authors.forename: Kristen
authors.initials: K
authors.lastname: DaSilva
authors.affiliation: Institute for Immunology and Informatics, University of Rhode Island, Providence, Rhode Island, United States of America; Division of Hematology and Oncology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island, United States of America.
authors.forename: Loren D
authors.initials: LD
authors.lastname: Fast
authors.affiliation: EpiVax, Inc., Providence, Rhode Island, United States of America.
authors.forename: Frances
authors.initials: F
authors.lastname: Terry
authors.affiliation: EpiVax, Inc., Providence, Rhode Island, United States of America.
authors.forename: William D
authors.initials: WD
authors.lastname: Martin
authors.affiliation: Institute for Immunology and Informatics, University of Rhode Island, Providence, Rhode Island, United States of America; EpiVax, Inc., Providence, Rhode Island, United States of America.
authors.forename: Anne S
authors.initials: AS
authors.lastname: De Groot
authors.affiliation: Institute for Immunology and Informatics, University of Rhode Island, Providence, Rhode Island, United States of America; EpiVax, Inc., Providence, Rhode Island, United States of America.
authors.forename: Leonard
authors.initials: L
authors.lastname: Moise
authors.affiliation: Division of Gastroenterology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island, United States of America.
authors.forename: Steven F
authors.initials: SF
authors.lastname: Moss
mesh_terms: D000595:Amino Acid Sequence; D019295:Computational Biology / Q000379:methods; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D058501:Enzyme-Linked Immunospot Assay; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D006681:HLA-D Antigens / Q000276:immunology*; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006681:HLA-D Antigens; D010455:Peptides; D007371:Interferon-gamma
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