Abstract
Abstract MHC Ib-restricted CD8+ T cells have been implicated to contribute to host defense during Mycobacteria tuberculosis (Mtb) infection, but the relative contribution of various MHC Ib-restricted responses has yet to be defined. In this study, we used mice that lack MHC Ia (Kb-/-Db-/-, DKO), MHC Ia/M3 (Kb-/-Db-/-M3-/-, TKO), or β2m (β2m-/-) to study the role of M3-restricted and other MHC Ib-restricted T cells in immunity against Mtb infection. Unlike their role in Listeria infection, we found that M3-restricted CD8+ T cells only represent a small proportion of the CD8+ T cells responding to Mtb infection. This finding highlights the differential role of various MHC Ib-restricted responses in immunity against distinct microbial pathogens. Non-M3, MHC Ib-restricted CD8+ T cells expanded preferentially in the lungs of TKO mice and expressed higher level of KLRG1 compared to MHC Ia-restricted CD8+ T cells. These CD8+ T cells produced IFNγ, TNFα and IL-2 upon stimulation with Mtb-derived protein antigens in a β2m-dependent but TAP-independent manner. TKO mice had similar bacterial loads in tissues as DKO and wildtype mice, but lower bacterial loads than β2m-/- mice. Our findings indicate non-M3, MHC Ib-restricted CD8+ T cells can specifically recognize Mtb protein antigens and contribute to host immune response to Mtb. Targeting these MHC Ib-restricted CD8+ T cells would facilitate the design of better vaccines against Mtb, due to the limited polymorphism of MHC class Ib molecules.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.