Presentation of Listeria monocytogenes antigens by major histocompatibility complex class I molecules to CD8 cytotoxic T lymphocytes independent of listeriolysin secretion and virulence.
Virulence and intracellular persistence of Listeria monocytogenes markedly depend on secretion of listeriolysin (Hly), which promotes invasion of the pathogen from the endosome into the cytosol. Recent studies have provided compelling evidence that Hly also facilitates recognition of listerial antigens, in association with major histocompatibility complex (MHC) class I molecules, by CD8 T lymphocytes. Data presented here confirm that the Hly-deficient strains, the prfA- mutant L. monocytogenes SLCC53 and the transposon mutants L. monocytogenes M3 and M20 are avirulent for mice, and unable to replicate inside bone marrow-derived macrophages (BMM phi). Furthermore, BMM phi infected with M3, M20 or SLCC53 were as efficiently lysed as BMM phi infected with the Hly-positive wild-type strain EGD by MHC class I-dependent CD8 cytotoxic T lymphocytes. Using the highly sensitive polymerase chain reaction method, hly mRNA was detectable in BMM phi infected with L. monocytogenes EGD or SLCC53, but totally absent in M3-infected BMM phi. In the case of M20, an excision of the transposon occurred, but the excision was not precise and the hly gene was approximately 400 base pairs shorter. These findings argue against a unique role for Hly in MHC class I presentation of listerial antigens, although Hly appears central to virulence and intracellular replication. Thus, virulence of L. monocytogenes is dissociable from MHC class I presentation of listerial antigens.
Department of Immunology, University of Ulm, FRG.
G
G
Szalay
J
J
Hess
S H
SH
Kaufmann
D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology*; D001427:Bacterial Toxins; D001483:Base Sequence; D016827:CD8 Antigens / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000502:physiology*; D006460:Hemolysin Proteins; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology* / Q000472:pathogenicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014774:Virulence / Q000502:physiology
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D016827:CD8 Antigens; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger; C038705:hlyA protein, Listeria monocytogenes