Nonclassical MHC Ib-restricted CD8+ T Cells Recognize Mycobacterium tuberculosis-Derived Protein Antigens and Contribute to Protection Against Infection

MHC Ib-restricted CD8+ T cells have been implicated in host defense against Mycobacterium tuberculosis (Mtb) infection. However, the relative contribution of various MHC Ib-restricted T cell populations to anti-mycobacterial immunity remains elusive. In this study, we used mice that lack MHC Ia (Kb-...

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Bibliographic Details
Published in:PLoS pathogens 2016-06, Vol.12 (6), p.e1005688-e1005688
Main Authors: Shang, Shaobin, Siddiqui, Sarah, Bian, Yao, Zhao, Jie, Wang, Chyung-Ru
Format: Article
Language:English
Subjects:
Animals
Antigens
Antigens, Bacterial - immunology
Biology and Life Sciences
CD8-Positive T-Lymphocytes - immunology
Cytokines
Cytotoxicity, Immunologic - immunology
Disease Models, Animal
Experiments
Flow Cytometry
Histocompatibility Antigens Class I
Infections
Listeria
Lungs
Lymphocytes
Medicine and Health Sciences
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Mycobacterium tuberculosis
Mycobacterium tuberculosis - immunology
Proteins
Real-Time Polymerase Chain Reaction
T-Lymphocyte Subsets - immunology
Tuberculosis
Tuberculosis - immunology
Vaccines
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Summary:MHC Ib-restricted CD8+ T cells have been implicated in host defense against Mycobacterium tuberculosis (Mtb) infection. However, the relative contribution of various MHC Ib-restricted T cell populations to anti-mycobacterial immunity remains elusive. In this study, we used mice that lack MHC Ia (Kb-/-Db-/-), MHC Ia/H2-M3 (Kb-/-Db-/-M3-/-), or β2m (β2m-/-) to study the role of M3-restricted and other MHC Ib-restricted T cells in immunity against Mtb. Unlike their dominant role in Listeria infection, we found that M3-restricted CD8+ T cells only represented a small proportion of the CD8+ T cells responding to Mtb infection. Non-M3, MHC Ib-restricted CD8+ T cells expanded preferentially in the lungs of Mtb-infected Kb-/-Db-/-M3-/- mice, exhibited polyfunctional capacities and conferred protection against Mtb. These MHC Ib-restricted CD8+ T cells recognized several Mtb-derived protein antigens at a higher frequency than MHC Ia-restricted CD8+ T cells. The presentation of Mtb antigens to MHC Ib-restricted CD8+ T cells was mostly β2m-dependent but TAP-independent. Interestingly, a large proportion of Mtb-specific MHC Ib-restricted CD8+ T cells in Kb-/-Db-/-M3-/- mice were Qa-2-restricted while no considerable numbers of MR1 or CD1-restricted Mtb-specific CD8+ T cells were detected. Our findings indicate that nonclassical CD8+ T cells other than the known M3, CD1, and MR1-restricted CD8+ T cells contribute to host immune responses against Mtb infection. Targeting these MHC Ib-restricted CD8+ T cells would facilitate the design of better Mtb vaccines with broader coverage across MHC haplotypes due to the limited polymorphism of MHC class Ib molecules.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1005688