Human CD8 T lymphocytes recognize Mycobacterium tuberculosis antigens presented by HLA-E during active tuberculosis and express type 2 cytokines

CD8 Tcells contribute to protective immunity against Mycobacterium tuberculosis. In humans, M. tuberculosis reactive CD8 Tcells typically recognize peptides associated to classical MHC class Ia molecules, but little information is available on CD8 Tcells recognizing M. tuberculosis Ags presented by nonclassical MHC class Ib molecules. We show here that CD8 Tcells from tuberculosis (TB) patients recognize HLA-E-binding M. tuberculosis peptides in a CD3/TCR mediated and CD8-dependent manner, and represent an additional type of effector cells playing a role in immune response to M. tuberculosis during active infection. HLA-E-restricted recognition of M. tuberculosis peptides is detectable by a significant enhanced ex vivo frequency of tetramer-specific circulating CD8 Tcells during active TB. These CD8 Tcells produce type 2 cytokines upon antigenic in vitro stimulation, help B cells for Ab production, and mediate limited TRAIL-dependent cytolytic and microbicidal activity toward M. tuberculosis infected target cells. Our results, together with the finding that HLA-E/M. tuberculosis peptide specific CD8 Tcells are detected in TB patients with or without HIV coinfection, suggest that this is a new human T-cell population that participates in immune response in TB.