MHC Ib molecule Qa-1 presents Mycobacterium tuberculosis peptide antigens to CD8+T cells and contributes to protection against infection

A number of nonclassical mhc ib molecules recognizing distinct microbial antigens have been implicated in the immune response to mycobacterium tuberculosis (mtb). hla-e has been identified to present numerous mtb peptides to cd8+t cells,with multiple hla-e-restricted cytotoxic t lymphocyte (ctl) and regulatory t cell lines isolated from patients with active and latent tuberculosis (tb). in other disease models,hla-e and its mouse homolog qa-1 can act as antigen presenting molecules as well as regulators of the immune response. however,it is unclear what precise role(s) hla-e/qa-1 play in the immune response to mtb. in this study,we found that murine qa-1 can bind and present mtb peptide antigens to cd8+t effector cells during aerosol mtb infection. further,mice lacking qa-1 (qa-1-/-) were more susceptible to high-dose mtb infection compared to wild-type controls,with higher bacterial burdens and increased mortality. the increased susceptibility of qa-1-/-mice was associated with dysregulated t cells that were more activated and produced higher levels of pro-inflammatory cytokines. t cells from qa-1-/-mice also had increased expression of inhibitory and apoptosis-associated cell surface markers such as cd94/nkg2a,klrg1,pd-1,fas-l,and ctla-4. as such,they were more prone to cell death and had decreased capacity in promoting the killing of mtb in infected macrophages. lastly,comparing the immune responses of qa-1 mutant knock-in mice deficient in either qa-1-restricted cd8+tregs(qa-1 d227k) or the inhibitory qa-1-cd94/nkg2a interaction (qa-1 r72a) with qa-1-/-and wild-type controls indicated that both of these qa-1-mediated mechanisms were involved in suppression of the immune response in mtb infection. our findings reveal that qa-1 participates in the immune response to mtb infection by presenting peptide antigens as well as regulating immune responses,resulting in more effective anti-mtb immunity. © 2017 bian et al.