A broad profile of co-dominant epitopes shapes the peripheral Mycobacterium tuberculosis specific CD8+ T-Cell immune response in South African patients with active tuberculosis

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dc.contributor.authorAxelsson-Robertson, Rebeccaen_ZA
dc.contributor.authorLoxton, Andre G.en_ZA
dc.contributor.authorWalzl, Gerharden_ZA
dc.contributor.authorEhlers, Marthie M.en_ZA
dc.contributor.authorKock, Marleen M.en_ZA
dc.contributor.authorZumla, Alimuddinen_ZA
dc.contributor.authorMaeurer, Markusen_ZA
dc.date.accessioned2014-07-07T12:18:39Z
dc.date.available2014-07-07T12:18:39Z
dc.date.issued2013-03-26
dc.descriptionCITATION: Axelsson-Robertson, R. et al. 2013. A broad profile of co-dominant epitopes shapes the peripheral Mycobacterium tuberculosis specific CD8+ T-Cell immune response in South African patients with active tuberculosis. PLoS ONE, 8(3): e58309, doi:10.1371/journal.pone.0058309.
dc.descriptionThe original publication is available at http://journals.plos.org
dc.description.abstractWe studied major histocompatibility complex (MHC) class I peptide-presentation and nature of the antigen-specific CD8+ T-cell response from South African tuberculosis (TB) patients with active TB. 361 MHC class I binding epitopes were identified from three immunogenic TB proteins (ESAT-6 [Rv3875], Ag85B [Rv1886c], and TB10.4 [Rv0288], including amino acid variations for Rv0288, i.e., A10T, G13D, S27N, and A71S for MHC allotypes common in a South African population (e.g., human leukocyte antigen [HLA]-A*30, B*58, and C*07). Inter-allelic differences were identified regarding the broadness of the peptide-binding capacity. Mapping of frequencies of Mycobacterium tuberculosis (M. tb) antigen-specific CD8+ T-cells using 48 different multimers, including the newly constructed recombinant MHC class I alleles HLA-B*58:01 and C*0701, revealed a low frequency of CD8+ T-cell responses directed against a broad panel of co-dominant M. tb epitopes in the peripheral circulation of most patients. The antigen-specific responses were dominated by CD8+ T-cells with a precursor-like phenotype (CD45RA+CCR7+). The data show that the CD8+ T-cell response from patients with pulmonary TB (prior to treatment) is directed against subdominant epitopes derived from secreted and non-secreted M. tb antigens and that variant, natural occurring M. tb Rv0288 ligands, have a profound impact on T-cell recognition.
dc.description.urihttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0058309
dc.description.versionPublisher's version
dc.format.extent15 pages
dc.identifier.citationAxelsson-Robertson, R. et al. 2013. A broad profile of co-dominant epitopes shapes the peripheral Mycobacterium tuberculosis specific CD8+ T-Cell immune response in South African patients with active tuberculosis. PLoS ONE, 8(3): e58309, doi:10.1371/journal.pone.0058309.
dc.identifier.issn1932-6203 (online)
dc.identifier.issn1932-6203 (print)
dc.identifier.otherdoi:10.1371/journal.pone.0058309
dc.identifier.urihttp://hdl.handle.net/10019.1/93396
dc.language.isoen_ZA
dc.publisherPublic Library of Science
dc.rights.holderAuthors retain copyright
dc.subjectMycobacterium tuberculosisen_ZA
dc.subjectMajor histocompatibility complexen_ZA
dc.subjectPeptidesen_ZA
dc.subjectCD Antigen -- Immunologyen_ZA
dc.subjectT cells -- Effect of drugs onen_ZA
dc.subjectImmunogeneticsen_ZA
dc.subjectAntigenic deternimantsen_ZA
dc.titleA broad profile of co-dominant epitopes shapes the peripheral Mycobacterium tuberculosis specific CD8+ T-Cell immune response in South African patients with active tuberculosisen_ZA
dc.typeArticle
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