Conserved immune recognition hierarchy of mycobacterial PE/PPE proteins during infection in natural hosts

dc.contributor.authorVordermeier, H Martinen_ZA
dc.contributor.authorHewinson, R Glynen_ZA
dc.contributor.authorWilkinson, Robert Jen_ZA
dc.contributor.authorWilkinson, Katalin Aen_ZA
dc.contributor.authorGideon, Hannah Pen_ZA
dc.contributor.authorYoung, Douglas Ben_ZA
dc.contributor.authorSampson, Samantha Len_ZA
dc.date.accessioned2015-12-28T06:47:43Z
dc.date.available2015-12-28T06:47:43Z
dc.date.issued2012en_ZA
dc.description.abstractThe Mycobacterium tuberculosis genome contains two large gene families encoding proteins of unknown function, characterized by conserved N-terminal proline and glutamate (PE and PPE) motifs. The presence of a large number of PE/PPE proteins with repetitive domains and evidence of strain variation has given rise to the suggestion that these proteins may play a role in immune evasion via antigenic variation, while emerging data suggests that some family members may play important roles in mycobacterial pathogenesis. In this study, we examined cellular immune responses to a panel of 36 PE/PPE proteins during human and bovine infection. We observed a distinct hierarchy of immune recognition, reflected both in the repertoire of PE/PPE peptide recognition in individual cows and humans and in the magnitude of IFN-γ responses elicited by stimulation of sensitized host cells. The pattern of immunodominance was strikingly similar between cattle that had been experimentally infected with Mycobacterium bovis and humans naturally infected with clinical isolates of M. tuberculosis. The same pattern was maintained as disease progressed throughout a four-month course of infection in cattle, and between humans with latent as well as active tuberculosis. Detailed analysis of PE/PPE responses at the peptide level suggests that antigenic cross-reactivity amongst related family members is a major determinant in the observed differences in immune hierarchy. Taken together, these results demonstrate that a subset of PE/PPE proteins are major targets of the cellular immune response to tuberculosis, and are recognized at multiple stages of infection and in different disease states. Thus this work identifies a number of novel antigens that could find application in vaccine development, and provides new insights into PE/PPE biology.en_ZA
dc.identifier.apacitationVordermeier, H. M., Hewinson, R. G., Wilkinson, R. J., Wilkinson, K. A., Gideon, H. P., Young, D. B., & Sampson, S. L. (2012). Conserved immune recognition hierarchy of mycobacterial PE/PPE proteins during infection in natural hosts. <i>PLoS One</i>, http://hdl.handle.net/11427/16045en_ZA
dc.identifier.chicagocitationVordermeier, H Martin, R Glyn Hewinson, Robert J Wilkinson, Katalin A Wilkinson, Hannah P Gideon, Douglas B Young, and Samantha L Sampson "Conserved immune recognition hierarchy of mycobacterial PE/PPE proteins during infection in natural hosts." <i>PLoS One</i> (2012) http://hdl.handle.net/11427/16045en_ZA
dc.identifier.citationVordermeier, H. M., Hewinson, R. G., Wilkinson, R. J., Wilkinson, K. A., Gideon, H. P., Young, D. B., & Sampson, S. L. (2012). Conserved immune recognition hierarchy of mycobacterial PE/PPE proteins during infection in natural hosts. PloS one, 7(8), e40890. doi:10.1371/journal.pone.0040890en_ZA
dc.identifier.ris TY - Journal Article AU - Vordermeier, H Martin AU - Hewinson, R Glyn AU - Wilkinson, Robert J AU - Wilkinson, Katalin A AU - Gideon, Hannah P AU - Young, Douglas B AU - Sampson, Samantha L AB - The Mycobacterium tuberculosis genome contains two large gene families encoding proteins of unknown function, characterized by conserved N-terminal proline and glutamate (PE and PPE) motifs. The presence of a large number of PE/PPE proteins with repetitive domains and evidence of strain variation has given rise to the suggestion that these proteins may play a role in immune evasion via antigenic variation, while emerging data suggests that some family members may play important roles in mycobacterial pathogenesis. In this study, we examined cellular immune responses to a panel of 36 PE/PPE proteins during human and bovine infection. We observed a distinct hierarchy of immune recognition, reflected both in the repertoire of PE/PPE peptide recognition in individual cows and humans and in the magnitude of IFN-γ responses elicited by stimulation of sensitized host cells. The pattern of immunodominance was strikingly similar between cattle that had been experimentally infected with Mycobacterium bovis and humans naturally infected with clinical isolates of M. tuberculosis. The same pattern was maintained as disease progressed throughout a four-month course of infection in cattle, and between humans with latent as well as active tuberculosis. Detailed analysis of PE/PPE responses at the peptide level suggests that antigenic cross-reactivity amongst related family members is a major determinant in the observed differences in immune hierarchy. Taken together, these results demonstrate that a subset of PE/PPE proteins are major targets of the cellular immune response to tuberculosis, and are recognized at multiple stages of infection and in different disease states. Thus this work identifies a number of novel antigens that could find application in vaccine development, and provides new insights into PE/PPE biology. DA - 2012 DB - OpenUCT DO - 10.1371/journal.pone.0040890 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2012 T1 - Conserved immune recognition hierarchy of mycobacterial PE/PPE proteins during infection in natural hosts TI - Conserved immune recognition hierarchy of mycobacterial PE/PPE proteins during infection in natural hosts UR - http://hdl.handle.net/11427/16045 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16045
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0040890
dc.identifier.vancouvercitationVordermeier HM, Hewinson RG, Wilkinson RJ, Wilkinson KA, Gideon HP, Young DB, et al. Conserved immune recognition hierarchy of mycobacterial PE/PPE proteins during infection in natural hosts. PLoS One. 2012; http://hdl.handle.net/11427/16045.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© Vordermeier et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherImmune responseen_ZA
dc.subject.otherCattleen_ZA
dc.subject.otherT cellsen_ZA
dc.subject.otherAntigensen_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.subject.otherGene poolen_ZA
dc.subject.otherCross reactivityen_ZA
dc.subject.otherMycobacterium bovisen_ZA
dc.titleConserved immune recognition hierarchy of mycobacterial PE/PPE proteins during infection in natural hostsen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
Vordermeier_Conserved_Immune_Recognition_2012.pdf
Size:
1.75 MB
Format:
Adobe Portable Document Format
Description:
Collections