How MAIT cells control the growth of intracellular mycobacteria (P4381)

Abstract Mucosal associated invariant T cells or MAIT cells have a semi-invariant TCR Vα chain and limited Vβ chains. In addition MAIT cell development is dependent upon the commensal microbiota and the expression of MR1, a highly conserved class Ib molecule of mammals. Mouse and human MAIT cells are activated in an MR1-restricted manner by cells infected with diverse strains for bacteria suggesting a widely shared antigen. Remarkably, human MR1 was recently shown to bind select bacterial vitamin B metabolites capable of activating MAIT cells in an MR1-restricted manner. This finding raised the interesting question of the importance of MR1 presentation of vitamin B metabolites for controlling bacterial infection. To address this question we have developed a mouse model whereby mycobacteria infected macrophages are co-cultured with purified MAIT cells, and control of intracellular bacterial growth is monitored. Using this assay, MAIT cell control of mycobacterial growth was found to depend upon IL-12 secretion by infected macrophages and IFN-γ secretion by MAIT cells. Interestingly, in the absence of infection, MAIT cells secreted IFN-γ in response to recombinant IL-12 alone or antigenic vitamin B metabolites. These findings demonstrate that MAIT cells can be activated by either TCR or non-TCR interactions. The contribution of these two pathways of MAIT cell activation in the context of mycobacterial infection is currently being investigated.