Qa-1b has antigen presentation and immunoregulatory roles during aerogenic Mycobacterium tuberculosis infection (P3296)

Abstract

Abstract The mouse MHC Ib molecule Qa-1b plays roles in both antigen presentation and immune regulation in different disease models. Further, the human homologue of Qa-1b, HLA-E, can present Mycobacterium tuberculosis (Mtb) peptides to CD8+ T cells. In viral infections, Qa-1b suppresses NK and CD8+ T cell function by interacting with inhibitory CD94/NKG2A molecules. In addition, Qa-1b can activate CD8+ T regulatory cells, which suppress CD4+ T cell responses in EAE. However, the role of Qa-1b in Mycobacterium tuberculosis (Mtb) infection is unknown. In this study, we find Qa-1b expression is upregulated in a mouse model of low-dose, aerogenic infection with Mtb. We find that Qa-1b, like HLA-E, can bind a number of Mtb peptides; a subset of these peptides are recognized by CD8+ T cells and induce IFN-γ production during aerogenic Mtb infection. To determine the overall contribution of Qa-1b to Mtb infection, we infected Qa-1b-deficient and wild-type mice. Qa-1b-deficient mice had increased production of pro-inflammatory cytokines compared to wild-type, indicating Qa-1b plays a regulatory role in Mtb infection. Infected Qa-1b-deficient mice also show increased expression of CD94/NKG2A on CD8+ T cells, indicating a potential mechanism by which Qa-1b controls immune responses in Mtb infection. Our data suggest that during Mtb infection, Qa-1b is uniquely able to both activate immune responses through antigen presentation as well as suppress immune responses via regulatory mechanisms.