PMID- 23555576
OWN - NLM
STAT- MEDLINE
DCOM- 20130930
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 3
DP  - 2013
TI  - 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.
PG  - e58309
LID - 10.1371/journal.pone.0058309 [doi]
LID - e58309
AB  - 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]-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.
FAU - Axelsson-Robertson, Rebecca
AU  - Axelsson-Robertson R
AD  - Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 
      Stockholm, Sweden.
FAU - Loxton, Andre G
AU  - Loxton AG
FAU - Walzl, Gerhard
AU  - Walzl G
FAU - Ehlers, Marthie M
AU  - Ehlers MM
FAU - Kock, Marleen M
AU  - Kock MM
FAU - Zumla, Alimuddin
AU  - Zumla A
FAU - Maeurer, Markus
AU  - Maeurer M
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20130326
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B*58:01 antigen)
RN  - 0 (HLA-C Antigens)
SB  - IM
MH  - Adult
MH  - Antigens, Bacterial/*immunology
MH  - CD8-Positive T-Lymphocytes/*immunology/pathology
MH  - Epitopes, T-Lymphocyte/*immunology
MH  - Female
MH  - HLA-B Antigens/*immunology
MH  - HLA-C Antigens/*immunology
MH  - Humans
MH  - Male
MH  - Mycobacterium tuberculosis/*immunology
MH  - South Africa
MH  - Tuberculosis, Pulmonary/epidemiology/*immunology/pathology
PMC - PMC3608651
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2013/04/05 06:00
MHDA- 2013/10/01 06:00
PMCR- 2013/03/26
CRDT- 2013/04/05 06:00
PHST- 2012/11/16 00:00 [received]
PHST- 2013/02/01 00:00 [accepted]
PHST- 2013/04/05 06:00 [entrez]
PHST- 2013/04/05 06:00 [pubmed]
PHST- 2013/10/01 06:00 [medline]
PHST- 2013/03/26 00:00 [pmc-release]
AID - PONE-D-12-35626 [pii]
AID - 10.1371/journal.pone.0058309 [doi]
PST - ppublish
SO  - PLoS One. 2013;8(3):e58309. doi: 10.1371/journal.pone.0058309. Epub 2013 Mar 26.