A Dominant CD4+ T-Cell Response to Helicobacter pylori Reduces Risk for Gastric Disease in Humans

Background & Aims Immunodominance is an important feature of antiviral, antitumor, and antibacterial cellular immune responses, but it is not well demonstrated in the immune responses against Helicobacter pylori . Antigen-specific CD4 + T cells protect mice against infection with H pylori . We investigated the immunodominant CD4 + T-cell response to neuraminyllactose-binding hemagglutinin (HpaA), which is a conserved, H pylori –specific colonization factor that is being investigated as an antigen for vaccination strategies. Methods HpaA-specific CD4 + T cells were expanded with autologous peripheral blood mononuclear cells that had been incubated with recombinant HpaA and characterized using overlapping synthetic peptides. We compared the percentage of CD4 + T cells with specificity for HpaA 88–100 , restricted to HLA-DRB1*1501, among 59 H pylori –infected subjects with different gastric diseases. Results We identified and characterized several immunodominant CD4 + T-cell epitopes derived from HpaA. The immunodominant CD4 + T-cell responses specific to HpaA 88–100 were observed in most H pylori –infected individuals who expressed HLA-DRB1*1501 and were significantly more abundant in patients with less severe diseases ( P Conclusions The HLA-DRB1*1501–restricted immunodominant CD4 + T-cell response to HpaA 88–100 is associated with reduced risk of severe gastric diseases. Further study of these and other immunodominant CD4 + T-cell responses to H pylori will provide insight into mechanisms of protective immunity and aid in vaccine design.