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Mucosal-associated invariant T (MAIT) cells represent a class of antimicrobial innate-like T cells that have been characterized in human blood, liver, lungs and intestine. Here, we investigated, for the first time, the presence of MAIT cells in the stomach of children, adults and the elderly undergoing routine endoscopy and assessed their reactivity to Helicobacter pylori (H. pylori-Hp), a major gastric pathogen. We observed that MAIT cells are present in the lamina propria compartment of the stomach and display a similar memory phenotype to blood MAIT cells. We then demonstrated that gastric and blood MAIT cells are able to recognize H. pylori. We found that CD8+ and CD4-CD8- (DN) MAIT cell subsets respond to H. pylori-infected macrophages stimulation in a MR-1 restrictive manner by producing cytokines (IFNg, TNFa, IL-17A) and exhibiting cytotoxic activity. Interestingly, we observed that blood MAIT cell frequency in Hp+ve individuals was significantly lower than in Hp-ve individuals. However, gastric MAIT cell frequency was not significantly different between Hp+ve and Hp-ve individuals, demonstrating a dichotomy between blood and gastric tissues. Further, we observed that the majority of gastric MAIT cells (>80%) expressed tissue-resident markers (CD69+ CD103+), which were only marginally present on PBMC MAIT cells (