Intestinal immunity plays critical roles in maintaining host health. Despite the abundance of foreign antigens and activated lymphocytes in the intestine, only a few commensal bacteria that induce cognate adaptive immune responses during homeostasis have been identified. In this dissertation, I reveal that Akkermansia muciniphila, an intestinal bacterium associated with beneficial effects on host metabolism and cancer immunotherapy, induces cognate T-dependent immunoglobulin G1 (IgG1) and IgA antibody responses and antigen-specific T cell responses during homeostasis. In contrast to the select few examples of previously characterized mucosal responses to commensal bacteria, T cell responses to A. muciniphila are limited to T follicular helper cells in the Peyer’s patches in a gnotobiotic setting, without appreciable induction of other T helper fates or migration to the lamina propria. However, A. muciniphila-specific responses are context-dependent, and adopt other T helper fates in the setting of a conventional microbiota. These findings suggest that contextual signals influence T cell immunity to the microbiota and modulate host immune function during homeostasis. Interestingly, T cells specific to A. muciniphila expand dramatically in a novel (but still uncharacterized) genetic mouse model of intestinal inflammation, suggesting that this bacterium may become a major mucosal antigen when homeostasis is disrupted. If so, T cell immunity to A. muciniphila may play critical roles during infection and inflammatory bowel diseases
