The role of MHC Ib in selecting functional CD8 T cell during acute LCMV infection (36.38)

Abstract

Abstract Conventional MHC Ia & II molecules (H-2K/D/L & I-A/E in mouse) select α/β CD8 & CD4 T cell development, respectively. Although unconventional MHC class Ib, mainly encoded in H-2 Q, T & M regions in mouse, contains more than 20 MHC Ib genes, their functions remain largely unknown. We developed a mouse model, in which 3 genes, Kb, Db & CIITA were deleted, thus called triple knock-out (TKO) mouse. In TKO, CD8 T cells are selected only by MHC Ib. Previously we have shown that α/β CD8 T cells develop well in TKO. Functionally, we observe that TKO mice mount a protective immune response against in vivo acute infections of LCMV. The protection is CD8 T cell mediated & β2m dependent. Rapid production of IFNγ and Granzyme B is detected in expended CD8 cells. Intriguingly, TKO mice do not appear to mount a memory response to a second infection. We report that splenocytes, from in vivo LCMV primed TKO, can be restimulated in vitro, by LCMV infected peritoneal macrophages or bone marrow derived dendritic cells, to produce IFNγ, but little IL-2. This MHC Ib-dependent response appears to be partially mediated by Qa-2. Therefore we have established an in vitro system to analyze MHC Ib-restricted T cell responses to LCMV & we are attempting to map the MHC Ib restriction element(s) and target epitopes. Collectively, our results suggest that MHC Ib can select functional CD8 T cells & these T cells participate in, at least under some circumstances, protective immune responses to pathogens.