-Specific HLA-E-Restricted T Cells Are Induced during Infection but Not after BCG Administration in Non-Human Primates and Humans.

Novel vaccines targeting the world's deadliest pathogen () are urgently needed as the efficacy of the Bacillus Calmette-Guérin (BCG) vaccine in its current use is limited. HLA-E is a virtually monomorphic unconventional antigen presentation molecule, and HLA-E-restricted -specific CD8 T cells can control intracellular growth, making HLA-E a promising vaccine target for . In this study, we evaluated the frequency and phenotype of HLA-E-restricted -specific CD4/CD8 T cells in the circulation and bronchoalveolar lavage fluid of two independent non-human primate (NHP) studies and from humans receiving BCG either intradermally or mucosally. BCG vaccination followed by challenge in NHPs did not affect the frequency of circulating and local HLA-E- CD4 and CD8 T cells, and we saw the same in humans receiving BCG. HLA-E- T cell frequencies were significantly increased after challenge in unvaccinated NHPs, which was correlated with higher TB pathology. Together, HLA-E--restricted T cells are minimally induced by BCG in humans and rhesus macaques (RMs) but can be elicited after infection in unvaccinated RMs. These results give new insights into targeting HLA-E as a potential immune mechanism against TB.