Innate-like γδ T cell responses to mycobacterium Bacille Calmette-Guerin using the public Vγ2 repertoire in Macaca fascicularis

The Vγ2Vδ2 T cell subset responds to Bacille Calmette-Guerin (BCG) immunization in macaques and may be a component of protective immunity against tuberculosis. We characterized the effects of BCG on the Vγ2Vδ2 T cell receptor repertoire by comparing the starting population of Vγ2 chains in cynomolgus macaques with the repertoire found after priming or booster immunization with BCG. The starting repertoire was dominated by public Vγ2 chain sequences that were found repeatedly among unrelated animals. Primary exposure to BCG triggered expansion of cells expressing public Vγ2 chains and booster immunization was often associated with contraction of these same subsets. Thus, BCG-reactive Vγ2 chains were present at high frequency in the repertoire of mycobacteria-naïve macaques and they comprised the major response to primary or booster immunization. Normal selection processes that created the naïve Vγ2 repertoire in macaques, also encoded the capacity for rapid responses to mycobacteria. The unusual composition of a normal Vγ2 repertoire helps to explain the powerful γδ T cell responses to BCG immunization.