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Nonclassical MHC Ib-restricted CD8+ T Cells Recognize Mycobacterium
tuberculosis-Derived Protein Antigens and Contribute to Protection Against
Infection
#MMPMID27272249
Shang S
; Siddiqui S
; Bian Y
; Zhao J
; Wang CR
PLoS Pathog
2016[Jun]; 12
(6
): e1005688
PMID27272249
show ga
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 ?2m (?2m-/-) 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 ?2m-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.
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