To examine the role of T cell receptor (TCR) in γδ T cells in adaptive immunity, a macaque model was used to follow Vγ2Vδ2⁺ T cell responses to mycobacterial infections. These phosphoantigen-specific γδ T cells displayed major expansion during Mycobacterium bovis Bacille Calmette-Guérin (BCG) infection and a clear memory-type response after BCG reinfection. Primary and recall expansions of Vγ2Vδ2⁺ T cells were also seen during Mycobacterium tuberculosis infection of naı̈ve and BCG-vaccinated macaques, respectively. This capacity to rapidly expand coincided with a clearance of BCG bacteremia and immunity to fatal tuberculosis in BCG-vaccinated macaques. Thus, Vγ2Vδ2⁺ T cells may contribute to adaptive immunity to mycobacterial infections.