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-/-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. © 2016 shang et al.