PMID- 17429413
OWN - NLM
STAT- MEDLINE
DCOM- 20070709
LR  - 20070606
IS  - 1466-4879 (Print)
IS  - 1466-4879 (Linking)
VI  - 8
IP  - 4
DP  - 2007 Jun
TI  - Impact of MHC class I alleles on the M. tuberculosis antigen-specific CD8+ T-cell 
      response in patients with pulmonary tuberculosis.
PG  - 334-43
AB  - Challenged by scattered understanding of protective immunity to Mycobacterium 
      tuberculosis (MTB), we have mapped peptide epitopes to human leukocyte antigen 
      (HLA)-A*0101, A*0201, A*1101, A*2402, B*0702, B*0801 and B*1501 of the secreted 
      mycobacterial antigen Ag85B, a vaccine candidate that may be associated with 
      immune protection. Affinity (ED(50)) and half-life (t(1/2), off-rate) analysis 
      for individual peptide species on HLA-A and HLA-B molecules revealed binding 
      ranges between 10(-3) and 10(-7) M. After selection of the best matches, major 
      histocompatibility complex class I/peptide tetramer complexes were constructed to 
      measure the CD8+ T-cell responses directly ex vivo in peripheral blood 
      mononuclear cells (PBMC) derived from 57 patients with acute pulmonary 
      tuberculosis. Three patterns of (allele-) specific CD8+ recognition were 
      identified: (a). Focus on one dominant epitope with additional recognition of 
      several subdominant T-cell epitopes (HLA-A*0301, A*2402, B*0801 and B*1501); (b). 
      Co-dominant recognition of two distinct groups of peptides presented by 
      HLA-B*0702; and (c). Diverse and broad recognition of peptides presented by 
      HLA-A*0201. Peptides that bound with slow off-rates to class I alleles, that is 
      HLA-A*0201, were associated with low frequency of CD8+ T cells in PBMCs from 
      patients with tuberculosis. HLA-B alleles showed fast off-rates in peptide 
      binding and restricted high numbers (up to 6%) of antigen-specific CD8+ T cells 
      in patients with pulmonary tuberculosis.
FAU - Weichold, F F
AU  - Weichold FF
AD  - Aeras Global TB Vaccine Foundation, Bethesda, MD, USA.
FAU - Mueller, S
AU  - Mueller S
FAU - Kortsik, C
AU  - Kortsik C
FAU - Hitzler, W E
AU  - Hitzler WE
FAU - Wulf, M J
AU  - Wulf MJ
FAU - Hone, D M
AU  - Hone DM
FAU - Sadoff, J C
AU  - Sadoff JC
FAU - Maeurer, M J
AU  - Maeurer MJ
LA  - eng
PT  - Journal Article
DEP - 20070412
PL  - England
TA  - Genes Immun
JT  - Genes and immunity
JID - 100953417
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-B Antigens)
SB  - IM
MH  - Alleles
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cells, Cultured
MH  - *Epitope Mapping
MH  - Flow Cytometry
MH  - *Genes, MHC Class I
MH  - HLA-A Antigens/genetics/immunology
MH  - HLA-B Antigens/genetics/immunology
MH  - Humans
MH  - Mycobacterium tuberculosis/*immunology
MH  - Tuberculosis, Pulmonary/*genetics/*immunology/physiopathology
EDAT- 2007/04/13 09:00
MHDA- 2007/07/10 09:00
CRDT- 2007/04/13 09:00
PHST- 2007/04/13 09:00 [pubmed]
PHST- 2007/07/10 09:00 [medline]
PHST- 2007/04/13 09:00 [entrez]
AID - 6364392 [pii]
AID - 10.1038/sj.gene.6364392 [doi]
PST - ppublish
SO  - Genes Immun. 2007 Jun;8(4):334-43. doi: 10.1038/sj.gene.6364392. Epub 2007 Apr 
      12.