An MHC Class Ib-Restricted CD8+ T Cell Response to Lymphocytic Choriomeningitis Virus

Abstract

Conventional MHC class Ia-restricted CD8+ T cells play a dominant role in the host response to virus infections, but recent studies indicate that T cells with specificity for nonclassical MHC class Ib molecules may also participate in host defense. To investigate the potential role of class Ib molecules in anti-viral immune responses, Kb−/−Db−/−CIITA−/− mice lacking expression of MHC class Ia and class II molecules were infected with lymphocytic choriomeningitis virus (LCMV). These animals have a large class Ib-selected CD8+ T cell population and they were observed to mediate partial (but incomplete) virus clearance during acute LCMV infection as compared with Kb−/−Db−/−β2-microglobulin−/− mice that lack expression of both MHC class Ia and class Ib molecules. Infection was associated with expansion of splenic CD8+ T cells and induction of granzyme B and IFN-γ effector molecules in CD8+ T cells. Partial virus clearance was dependent on CD8+ cells. In vitro T cell restimulation assays demonstrated induction of a population of β2-microglobulin–dependent, MHC class Ib-restricted CD8+ T cells with specificity for viral Ags and yet to be defined nonclassical MHC molecules. MHC class Ib-restricted CD8+ T cell responses were also observed after infection of Kb−/−Db−/−mice despite the low number of CD8+ T cells in these animals. Long-term infection studies demonstrated chronic infection and gradual depletion of CD8+ T cells in Kb−/−Db−/−CIITA−/− mice, demonstrating that class Ia molecules are required for viral clearance. These findings demonstrate that class Ib-restricted CD8+ T cells have the potential to participate in the host immune response to LCMV.