H2-M3-restricted T cells in bacterial infection: Rapid primary but diminished memory responses

Major histocompatibility complex (MHC) class Ib molecules have been implica ted in CD8(+) T cell-mediated defenses against intracellular bacterial infe ction, but the relative importance of MHC class Ib-restricted T cells in an timicrobial immunity is unknown. In this report, we use MHC tetramers to ch aracterize T cell responses restricted by H2-M3, an MHC class Ib molecule t hat selectively presents N-formyl peptides. We find that sizeable H2-M3-res tricted 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 cytoly tic and produce interferon gamma. 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 ch aracterization of an MHC class Ib-restricted T cell response indicates that CD8(+) T cells responding to L. monocytogenes infection can be divided int o two groups: H2-M3-restricted responses, which provide rapid and quantitat ively substantial effector function during primary infections but contribut e relatively Little to memory responses, and MHC class Ia-restricted respon ses, which expand later during primary infection but form memory T cells th at respond rapidly and dramatically in response to subsequent infections by the same pathogen.