H2-M3 restricted T cell responses to bacterial infection

CD8+ T lymphocytes are important mediators of immune defense against many intracellular pathogens. Most CD8+ T cells recognize peptide antigen in the context of polymorphic MHC class Ia molecules; the role of these class Ia restricted lymphocytes in antimicrobial defenses against many viral and bacterial pathogens is well established. Some microbial antigen is presented to CD8+ T cells by members of the nonpolymorphic MHC class Ib family, but the relative importance of class Ib restricted T cells in antimicrobial immunity is unknown. One relatively well-characterized MHC class Ib molecule is the murine H2-M3 molecule, which selectively presents peptides with N-formyl methionine to CD8+ T cells. Because N-formylation is a hallmark of bacterial protein synthesis, H2-M3 seems particularly suitable for immune defense against bacterial infection. Using H2-M3 tetramers to detect epitope-specific T cells, we found that sizeable M3 restricted T cell populations, capable of both cytolysis and cytokine secretion, undergo expansion and peak in frequency earlier than MHC class Ia restricted T cells following primary infection with the intracellular bacterium Listeria monocytogenes. Although M3 restricted memory T cells are activated by a second Listeria infection, they undergo limited expansion in comparison to the dramatic expansion of MHC class Ia restricted cells. These data suggest that H2-M3 restricted CD8+ T lymphocytes make important contributions to antibacterial immunity in response to primary infection, but the role of this subset in immunological memory remains unclear. The early expansion of H2-M3 restricted T cell populations, together with a greater variability in the magnitudes of CD8+ T cell responses restricted by M3 than those restricted by the MHC class Ia molecule H2-Kd, also suggests that the repertoire of H2-M3 restricted T cells is influenced by the environment. This first direct characterization of an MHC class Ib restricted T cell response to bacterial infection demonstrates that H2-M3 restricted responses have attributes of both innate and adaptive immune responses and distinguishes them from MHC class Ia restricted T cell responses to infection.