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

Menée sur un modèle murin, cette étude analyse la réponse des lymphocytes T CD4+ à un antigène spécifique d'Helicobacter pylori visant à réduire le risque de cancer de l'estomac

Résumé en anglais

Immunodominance is an important feature of anti-viral, anti-tumor, and anti-bacterial cellular immune responses, but it is not well-demonstrated in the immune responses against Helicobacter pylori (H. 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)— a conserved, H. pylori -specific colonization factor that is being investigated as an antigen for vaccination strategies. HpaA-specific CD4+ T cells were expanded with autologous peripheral blood mononuclear cells (PBMCs) that had been incubated with recombinant HpaA, and characterized using overlapping synthetic peptides. We compared the percentage of CD4+ T cells with specificity for HpaA88-100, restricted to HLA-DRB1*1501, among 59 H. pylori -infected subjects with different gastric diseases. We identified and characterized several immunodominant CD4+ T cell epitopes derived from HpaA. The immunodominant CD4+ T-cell responses specific to HpaA88–100 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 <0.05). The HLA-DRB1*1501-restricted immunodominant CD4+ T-cell response to HpaA88-100 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 aide in vaccine design.