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Published online 6 February 2006 doi:10.1084/jem.20052256
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 2, 383-391
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ARTICLE

H2-M3–restricted CD8+ T cells are not required for MHC class Ib–restricted immunity against Listeria monocytogenes

Sarah E.F. D'Orazio1, Christine A. Shaw2, and Michael N. Starnbach2

1 Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536
2 Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115

CORRESPONDENCE Michael N. Starnbach: starnbach{at}hms.harvard.edu

Studies using major histocompatibility complex (MHC)-Ia–deficient mice have shown that MHC-Ib–restricted CD8+ T cells can clear infections caused by intracellular pathogens such as Listeria monocytogenes. M3-restricted CD8+ T cells, which recognize short hydrophobic N-formylated peptides, appear to comprise a substantial portion of the MHC-Ib–restricted T cell response in the mouse model of L. monocytogenes infection. In this study, we isolated formyltransferase (fmt) mutant strains of L. monocytogenes that lacked the ability to add formyl groups to nascent polypeptides. These fmt mutant Listeria strains did not produce antigens that could be recognized by M3-restricted T cells. We showed that immunization of MHC-Ia–deficient mice with fmt mutant Listeria resulted in stimulation of a protective memory response that cleared subsequent challenge with wild-type L. monocytogenes, despite the fact that M3-restricted CD8+ T cells did not proliferate in these mice. These data suggest that M3-restricted T cells are not required for protection against L. monocytogenes and underscore the importance of searching for new antigen-presenting molecules among the large MHC-Ib family of proteins.


Abbreviations used: ActR, actinonin-resistant; BHI, brain heart infusion; BMM{Phi}, bone marrow–derived macrophages; fmt, formyltransferase; ICCS, intracellular cytokine staining; MTF, methionyl-tRNAfMet formyltransferase; PDF, peptide deformlyase.


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