Human T cells recognize M. tuberculosis (Mtb) cell wall lipid antigens when bound to non-polymorphic CD1a, CD1b, and CD1c proteins on the surface of antigen presenting cells. The development of lipid-loaded CD1 tetramers has facilitated ex vivo studies of human CD1-restricted T cells in the setting of vaccination and tuberculosis (TB) disease. Since mice do not express CD1a, CD1b, or CD1c, we have leveraged the non-human primate (NHP) model to elucidate the role of CD1-restricted T cells in the pathogenesis of TB. Using an evolutionary genetic approach, we found a lack of diversifying selection in CD1 genes over 45 million years of primate evolution, which stands in stark contrast to the history of the MHC system for presenting peptide antigens to T cells. We developed and validated Macaca mulatta (Mamu) CD1 tetramers and showed that CD1-restricted T cells are expanded after intravenous BCG vaccination, which mediates near-sterilizing immunity to Mtb. Ongoing work seeks to use Mamu CD1 tetramers to uncover the in vivo functional profiles of CD1-restricted T cells and their role in mediating protection against TB.