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.

Interaction between inflammatory mediators and miRNAs in Helicobacter pylori infection

“…IL‐6 is the most abundant cytokine during prolonged and uncontrolled activation of inflammation (Mauer et al ., ). Overexpression of IL‐6 was reported in H. pylori infection by others studies (Zhao et al ., ; Zhang et al ., ). Concerning treatment effect, Ando et al .…”

T cell epitope redundancy: cross-conservation of the TCR face between pathogens and self and its implications for vaccines and autoimmunity

“…An EpiBar is a single 9-mer frame containing binding motifs for at least four different HLA alleles (Figure 3). In retrospective evaluations of published promiscuous epitopes, we have found this pattern to be a signature feature of highly immunogenic, promiscuous class II epitopes [53,54].…”

iVAX: An integrated toolkit for the selection and optimization of antigens and the design of epitope-driven vaccines

“…Significant advancements in immunome-derived, epitopedriven vaccines designed using the iVAX toolkit have been made in recent years; in particular, basic research studies have demonstrated the ability of the tools to select epitopes for Burkholderia species, 29 H. pylori 30 and HCV, [31][32][33] and validated the importance of the presence of T cell epitopes in subunit vaccines. Recently, the collaborating groups at EpiVax and iCubed discovered epitopes that activate T regulatory cells (Tregs) in viral pathogens using the JanusMatrix tool.…”