V9+V2+T cell control of Listeria monocytogenes growth in infected epithelial cells requires butyrophilin 3A genes

Intracellular bacteria produce antigens, which serve as potent activators of gamma delta T cells. Phosphoantigens are presented via a complex of butyrophilins (BTN) to signal infection to human V gamma 9+V delta 2+ T cells. Here, we established an in vitro system allowing for studies of V gamma 9+V delta 2+ T cell activity in coculture with epithelial cells infected with the intracellular bacterial pathogen Listeria monocytogenes. We report that the V gamma 9+V delta 2+ T cells efficiently control L. monocytogenes growth in such cultures. This effector function requires the expression of members of the BTN3A family on epithelial cells. Specifically, we observed a BTN3A1-independent BTN3A3 activity to present antigen to V gamma 9+V delta 2+ T cells. Since BTN3A1 is the only BTN3A associated with phosphoantigen presentation, our study suggests that BTN3A3 may present different classes of antigens to mediate V gamma 9+V delta 2+ T cell effector function against L. monocytogenes-infected epithelia.