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 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 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.
Kerksiek
K M
KM
Section of Infectious Diseases and Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Busch
D H
DH
Pilip
I M
IM
Allen
S E
SE
Pamer
E G
EG
D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017931:DNA Primers / Q000235:genetics; D000939:Epitopes / Q000737:chemistry; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000235:genetics; D007156:Immunologic Memory; D066298:In Vitro Techniques; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011487:Protein Conformation
D000942:Antigens, Bacterial; D017931:DNA Primers; D000939:Epitopes; D000949:Histocompatibility Antigens Class II