Mycobacterium tuberculosis peptides presented by HLA-E molecules are targets for human CD8 T-cells with cytotoxic as well as regulatory activity

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dc.contributor.authorJoosten, Simone Aen_ZA
dc.contributor.authorvan Meijgaarden, Krista Een_ZA
dc.contributor.authorvan Weeren, Pascale Cen_ZA
dc.contributor.authorKazi, Fatimaen_ZA
dc.contributor.authorGeluk, Annemiekeen_ZA
dc.contributor.authorSavage, Nigel D Len_ZA
dc.contributor.authorDrijfhout, Jan Wen_ZA
dc.contributor.authorFlower, Darren Ren_ZA
dc.contributor.authorHanekom, Willem Aen_ZA
dc.contributor.authorKlein, Michèl Ren_ZA
dc.date.accessioned2016-01-11T06:52:17Z
dc.date.available2016-01-11T06:52:17Z
dc.date.issued2010en_ZA
dc.description.abstractTuberculosis (TB) is an escalating global health problem and improved vaccines against TB are urgently needed. HLA-E restricted responses may be of interest for vaccine development since HLA-E displays very limited polymorphism (only 2 coding variants exist), and is not down-regulated by HIV-infection. The peptides from Mycobacterium tuberculosis (Mtb) potentially presented by HLA-E molecules, however, are unknown. Here we describe human T-cell responses to Mtb-derived peptides containing predicted HLA-E binding motifs and binding-affinity for HLA-E. We observed CD8+ T-cell proliferation to the majority of the 69 peptides tested in Mtb responsive adults as well as in BCG-vaccinated infants. CD8+ T-cells were cytotoxic against target-cells transfected with HLA-E only in the presence of specific peptide. These T cells were also able to lyse M. bovis BCG infected, but not control monocytes, suggesting recognition of antigens during mycobacterial infection. In addition, peptide induced CD8+ T-cells also displayed regulatory activity, since they inhibited T-cell proliferation. This regulatory activity was cell contact-dependent, and at least partly dependent on membrane-bound TGF-β. Our results significantly increase our understanding of the human immune response to Mtb by identification of CD8+ T-cell responses to novel HLA-E binding peptides of Mtb, which have cytotoxic as well as immunoregulatory activity.en_ZA
dc.identifier.apacitationJoosten, S. A., van Meijgaarden, K. E., van Weeren, P. C., Kazi, F., Geluk, A., Savage, N. D. L., ... Klein, M. R. (2010). Mycobacterium tuberculosis peptides presented by HLA-E molecules are targets for human CD8 T-cells with cytotoxic as well as regulatory activity. <i>PLoS One</i>, http://hdl.handle.net/11427/16263en_ZA
dc.identifier.chicagocitationJoosten, Simone A, Krista E van Meijgaarden, Pascale C van Weeren, Fatima Kazi, Annemieke Geluk, Nigel D L Savage, Jan W Drijfhout, Darren R Flower, Willem A Hanekom, and Michèl R Klein "Mycobacterium tuberculosis peptides presented by HLA-E molecules are targets for human CD8 T-cells with cytotoxic as well as regulatory activity." <i>PLoS One</i> (2010) http://hdl.handle.net/11427/16263en_ZA
dc.identifier.citationJoosten, S. A., Van Meijgaarden, K. E., Van Weeren, P. C., Kazi, F., Geluk, A., Savage, N. D., ... & Ottenhoff, T. H. (2010). Mycobacterium tuberculosis peptides presented by HLA-E molecules are targets for human CD8 T-cells with cytotoxic as well as regulatory activity. PLoS Pathog, 6(2), e1000782. doi:10.1371/journal.ppat.1000782en_ZA
dc.identifier.ris TY - Journal Article AU - Joosten, Simone A AU - van Meijgaarden, Krista E AU - van Weeren, Pascale C AU - Kazi, Fatima AU - Geluk, Annemieke AU - Savage, Nigel D L AU - Drijfhout, Jan W AU - Flower, Darren R AU - Hanekom, Willem A AU - Klein, Michèl R AB - Tuberculosis (TB) is an escalating global health problem and improved vaccines against TB are urgently needed. HLA-E restricted responses may be of interest for vaccine development since HLA-E displays very limited polymorphism (only 2 coding variants exist), and is not down-regulated by HIV-infection. The peptides from Mycobacterium tuberculosis (Mtb) potentially presented by HLA-E molecules, however, are unknown. Here we describe human T-cell responses to Mtb-derived peptides containing predicted HLA-E binding motifs and binding-affinity for HLA-E. We observed CD8+ T-cell proliferation to the majority of the 69 peptides tested in Mtb responsive adults as well as in BCG-vaccinated infants. CD8+ T-cells were cytotoxic against target-cells transfected with HLA-E only in the presence of specific peptide. These T cells were also able to lyse M. bovis BCG infected, but not control monocytes, suggesting recognition of antigens during mycobacterial infection. In addition, peptide induced CD8+ T-cells also displayed regulatory activity, since they inhibited T-cell proliferation. This regulatory activity was cell contact-dependent, and at least partly dependent on membrane-bound TGF-β. Our results significantly increase our understanding of the human immune response to Mtb by identification of CD8+ T-cell responses to novel HLA-E binding peptides of Mtb, which have cytotoxic as well as immunoregulatory activity. DA - 2010 DB - OpenUCT DO - 10.1371/journal.ppat.1000782 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2010 T1 - Mycobacterium tuberculosis peptides presented by HLA-E molecules are targets for human CD8 T-cells with cytotoxic as well as regulatory activity TI - Mycobacterium tuberculosis peptides presented by HLA-E molecules are targets for human CD8 T-cells with cytotoxic as well as regulatory activity UR - http://hdl.handle.net/11427/16263 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16263
dc.identifier.urihttp://dx.doi.org/10.1371/journal.ppat.1000782
dc.identifier.vancouvercitationJoosten SA, van Meijgaarden KE, van Weeren PC, Kazi F, Geluk A, Savage NDL, et al. Mycobacterium tuberculosis peptides presented by HLA-E molecules are targets for human CD8 T-cells with cytotoxic as well as regulatory activity. PLoS One. 2010; http://hdl.handle.net/11427/16263.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentSouth African Tuberculosis Vaccine Initiative (SATVI)en_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© 2010 Joosten et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plospathogensen_ZA
dc.subject.otherT cellsen_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.subject.otherCytotoxic T cellsen_ZA
dc.subject.otherCloningen_ZA
dc.subject.otherPeptide synthesisen_ZA
dc.subject.otherBinding analysisen_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherAntigen-presenting cellsen_ZA
dc.titleMycobacterium tuberculosis peptides presented by HLA-E molecules are targets for human CD8 T-cells with cytotoxic as well as regulatory activityen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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