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

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

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Title: MHC Ib molecule Qa-1 presents Mycobacterium tuberculosis peptide antigens to CD8+ T cells and contributes to protection against infection
Author: Bian, Yao; Shang, Shaobin; Siddiqui, Sarah; Zhao, Jie; Joosten, Simone A.; Ottenhoff, Tom H. M.; Cantor, Harvey; Wang, Chyung-Ru

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Citation: Bian, Yao, Shaobin Shang, Sarah Siddiqui, Jie Zhao, Simone A. Joosten, Tom H. M. Ottenhoff, Harvey Cantor, and Chyung-Ru Wang. 2017. “MHC Ib molecule Qa-1 presents Mycobacterium tuberculosis peptide antigens to CD8+ T cells and contributes to protection against infection.” PLoS Pathogens 13 (5): e1006384. doi:10.1371/journal.ppat.1006384. http://dx.doi.org/10.1371/journal.ppat.1006384.
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Abstract: 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.
Published Version: doi:10.1371/journal.ppat.1006384
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435364/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:33029708
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