MHC Ib-restricted T Cells Generate the Dominant Memory T Cell Response in Early Stages of <i>Mycobacterium tuberculosis</i>Infection

Abstract Unconventional T cells, which recognize monomorphic MHC Ib molecules, such as Qa1, Qa2, M3, CD1, and MR1 have been implicated in the primary response to Mycobacterium tuberculosis(Mtb) infection. However, whether these cells play a role molecules participate memory against Mtbinfection remains unknown. To determine optimal immunization strategy, we vaccinated mice that lack Ia (K b−/−D b−/−) with an attenuated MtbH37Rv strain via intravenous (IV) or subcutaneous (SC) injection. We found both routes of induced comparable Ib-restricted CD8 +T cell after virulent re-challenge. Since bacteria were cleared through SC but not IV route, selected our route immunization. produced multiple proinflammatory cytokines, expanded faster Mtbchallenge than those unvaccinated mice, recognized several Mtbprotein antigens. Importantly, was more dominant Ia-restricted at early stages also observed increased percentage number Qa2 M3-restricted infection, suggesting can elicit response. While CD1d-restricted NKT did differ significantly between non-vaccinated activation kinetics MR1-restricted accelerated mice. Overall, show important thus should be included subunit vaccine formulation. Supported by grants from NIH (R01AI141083)