H2-M3–Restricted T Cells in Bacterial Infection: Rapid Primary but Diminished Memory Responses

Major histocompatibility complex (MHC) class Ib molecules have been implicated in CD8⁺ T cell–mediated defenses against intracellular bacterial infection, but the relative importance of MHC class Ib–restricted T cells in antimicrobial immunity is unknown. In this report, we use MHC tetramers to characterize T cell responses restricted by H2-M3, an MHC class Ib molecule that selectively presents N-formyl peptides. We find that sizeable H2-M3–restricted T cell responses, occurring earlier than MHC class Ia–restricted T cell responses, are mounted after primary infection with the intracellular bacterium Listeria monocytogenes. These H2-M3–restricted T cells are cytolytic and produce interferon γ. However, after a second L. monocytogenes infection, H2-M3–restricted memory T cell responses are minor in comparison to the much larger MHC class Ia–restricted responses. This first direct characterization of an MHC class Ib–restricted T cell response indicates that CD8⁺ T cells responding to L. monocytogenes infection can be divided into two groups: H2-M3–restricted responses, which provide rapid and quantitatively substantial effector function during primary infections but contribute relatively little to memory responses, and MHC class Ia–restricted responses, which expand later during primary infection but form memory T cells that respond rapidly and dramatically in response to subsequent infections by the same pathogen.