Sensing mycobacteria through unconventional pathways.

Approximately one-quarter of the global population is estimated to be infected with Mycobacterium tuberculosis. New developments in vaccine design and therapeutics are urgently needed, particularly in the face of multidrug-resistant tuberculosis (TB). In this issue of the JCI, Sakai and colleagues used a multidisciplinary approach to determine that trehalose-6-monomycolate (TMM), a mycobacterial cell wall lipid, serves as a T cell antigen presented by CD1b. CD1b-TMM-specific T cells were characterized by conserved T cell receptor features and were present at elevated frequencies in individuals with active TB disease. These findings highlight the dual role of TMM in stimulating both innate and adaptive immunity and broaden our understanding of CD1-mediated lipid recognition by unconventional T cells.