T cell responses to Gram-negative intracellular bacterial pathogens: a role for CD8+ T cells in immunity to Salmonella infection and the involvement of MHC class Ib molecules.
Despite being a major group of intracellular pathogens, the role of class I-restricted T cells in the clearance of Gram-negative bacteria is not resolved. Using a murine typhoid model, a role for class I-restricted T cells in the immune response to the Gram-negative pathogen Salmonella typhimurium is revealed. Class I-deficient beta2-microglobulin-/- mice show increased susceptibility to infection with S. typhimurium. Following infection, CD8+ CTLs specific for Salmonella-infected targets can be readily detected. The Salmonella-specific CTLs recognize infected H-2-mismatched targets, suggesting the involvement of shared class Ib molecules. Studies using transfectants expressing defined class Ia and class Ib molecules indicate the involvement of the class Ib molecule, Qa-1. Ab-blocking studies and the measurement of bacteria-specific CTL frequencies identified Qa-1 as a dominant restricting element. The Qa-1-restricted CTL recognition depends on TAP and proteasome functions. Surprisingly, Qa-1-restricted CTLs recognized cells infected with other closely related Gram-negative bacteria. Taken together, these observations indicate that Salmonella-specific CTLs recognize a cross-reactive epitope presented by Qa-1 molecules and, as such, may be novel targets for vaccine development.
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WF
Division of Molecular and Clinical Rheumatology, Department of Medicine, Graduate Program in Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Ong
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H
Metcalf
E S
ES
Soloski
M J
MJ
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004198:Disease Susceptibility; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000382:microbiology
D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; C032907:Q surface antigens