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.

We 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], A...

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Autores principales:	Rebecca Axelsson-Robertson, André G Loxton, Gerhard Walzl, Marthie M Ehlers, Marleen M Kock, Alimuddin Zumla, Markus Maeurer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dedc158c14e64c5e9338702f7ad42074
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spelling	oai:doaj.org-article:dedc158c14e64c5e9338702f7ad420742021-11-18T07:52:05ZA broad profile of co-dominant epitopes shapes the peripheral Mycobacterium tuberculosis specific CD8+ T-cell immune response in South African patients with active tuberculosis.1932-620310.1371/journal.pone.0058309https://doaj.org/article/dedc158c14e64c5e9338702f7ad420742013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23555576/?tool=EBIhttps://doaj.org/toc/1932-6203We 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]-A30, B58, and C07). 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-B58:01 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.Rebecca Axelsson-RobertsonAndré G LoxtonGerhard WalzlMarthie M EhlersMarleen M KockAlimuddin ZumlaMarkus MaeurerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e58309 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rebecca Axelsson-Robertson André G Loxton Gerhard Walzl Marthie M Ehlers Marleen M Kock Alimuddin Zumla Markus Maeurer 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.
description	We 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]-A30, B58, and C07). 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-B58:01 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.
format	article
author	Rebecca Axelsson-Robertson André G Loxton Gerhard Walzl Marthie M Ehlers Marleen M Kock Alimuddin Zumla Markus Maeurer
author_facet	Rebecca Axelsson-Robertson André G Loxton Gerhard Walzl Marthie M Ehlers Marleen M Kock Alimuddin Zumla Markus Maeurer
author_sort	Rebecca Axelsson-Robertson
title	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.
title_short	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.
title_full	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.
title_fullStr	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.
title_full_unstemmed	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.
title_sort	broad profile of co-dominant epitopes shapes the peripheral mycobacterium tuberculosis specific cd8+ t-cell immune response in south african patients with active tuberculosis.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/dedc158c14e64c5e9338702f7ad42074
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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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