Unconventional T cell subsets, including donor-unrestricted T cells (DURTs) and γδ T cells, are promising new players in the treatment and prevention of infectious diseases. In this issue of the JCI, Ogongo et al. used T cell receptor (TCR) sequencing to characterize unconventional T cell subsets in surgical lung resections and blood from Mycobacterium tuberculosis-infected (Mtb-infected) individuals with and without HIV coinfection. The study revealed highly localized expansions of γδ T cell clonotypes not previously associated with the immune response to Mtb and demonstrates the power of high-throughput analysis of the TCR repertoire directly from infected tissue. The findings contribute to our understanding of tuberculosis control and have implications for the development of both therapeutic and vaccination strategies.