Helicobacter pylori induces urease subunit B-specific CD8+ T cell responses in infected individuals via cytosolic pathway of cross-presentation.

Abstract

Urease subunit B (UreB), a conserved and key virulence factor of Helicobacter pylori (H. pylori), can induce the host CD4+ T cell immune responses to provide protection, but less is known regarding CD8+ T cell responses. The characteristics of H. pylori-specific CD8+ T cell responses and the mechanism underlying antigen processing and presentation pathways remain unclear. This study was focus on protective antigen recombinant UreB (rUreb) to detect specific CD8+ T cell responses in vitro and elucidate the mechanism of UreB antigen processing and presentation. The peripheral blood mononuclear cells (PBMCs) collected from H. pylori-infected individuals were stimulated with rUreB in vitro to detect specific CD8+ T cell responses after co-culture with rUreB-pulsed autologous hMDCs. Through blocking assay, we investigated the potential pathway of UreB antigen processing and presentation via the cytosolic pathway or vacuolar pathway. The cytokines production of UreB specific CD8+ T cell were evaluated as well. We demonstrated UreB can induce specific CD8+ T cell immune responses in H. pylori infected individuals. Importantly, we characterized that UreB were mainly processed by proteasome instead of lysosomal proteases and presented through cytosolic pathway of cross-presentation, which requires endoplasmic reticulum-Golgi transport and newly synthesized MHC-I molecules, to induce functional-specific CD8+ T cell (IFN-γ + TNF-α + Grz A+ Grz B+) responses. These results suggest that H. pylori UreB induces specific CD8+ T cell responses through cytosolic pathway of cross-presentation in infected individuals.