Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2000-12-21
pubmed:abstractText
The role of CD8(+) CTL in protection against tuberculosis in human disease is unclear. In this study, we stimulated the peripheral blood mononuclear cells of bacillus Calmette-Guérin (BCG)-vaccinated individuals with live Mycobacterium bovis BCG bacilli to establish short-term cell lines and then purified the CD8(+) T cells. A highly sensitive enzyme-linked immunospot (ELISPOT) assay for single cell IFN-gamma release was used to screen CD8(+) T cells with overlapping peptides spanning the mycobacterial major secreted protein, Ag85A. Three peptides consistently induced a high frequency of IFN-gamma responsive CD8(+) T cells, and two HLA-A*0201 binding motifs, P(48-56) and P(242-250), were revealed within the core sequences. CD8(+) T cells responding to the 9-mer epitopes were visualized within fresh blood by ELISPOT using free peptide or by binding of HLA-A*0201 tetrameric complexes. The class I-restricted CD8(+) T cells were potent CTL effector cells that efficiently lysed an HLA-A2-matched monocyte cell line pulsed with peptide as well as autologous macrophages infected with Mycobacterium tuberculosis or recombinant vaccinia virus expressing the whole Ag85A protein. Tetramer assays revealed a 6-fold higher frequency of peptide-specific T cells than IFN-gamma ELISPOT assays, indicating functional heterogeneity within the CD8(+) T cell population. These results demonstrate a previously unrecognized, MHC class I-restricted, CD8(+) CTL response to a major secreted Ag of mycobacteria and supports the use of Ag85A as a candidate vaccine against tuberculosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
165
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7088-95
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11120838-Acyltransferases, pubmed-meshheading:11120838-Antigen Presentation, pubmed-meshheading:11120838-Antigens, Bacterial, pubmed-meshheading:11120838-BCG Vaccine, pubmed-meshheading:11120838-Cell Line, pubmed-meshheading:11120838-Cytotoxicity Tests, Immunologic, pubmed-meshheading:11120838-Epitope Mapping, pubmed-meshheading:11120838-Epitopes, T-Lymphocyte, pubmed-meshheading:11120838-Gambia, pubmed-meshheading:11120838-Great Britain, pubmed-meshheading:11120838-Humans, pubmed-meshheading:11120838-Immunophenotyping, pubmed-meshheading:11120838-Interferon-gamma, pubmed-meshheading:11120838-Interleukin-4, pubmed-meshheading:11120838-Lymphocyte Count, pubmed-meshheading:11120838-Mycobacterium tuberculosis, pubmed-meshheading:11120838-Oligopeptides, pubmed-meshheading:11120838-T-Lymphocyte Subsets, pubmed-meshheading:11120838-T-Lymphocytes, Cytotoxic, pubmed-meshheading:11120838-Tumor Cells, Cultured
pubmed:year
2000
pubmed:articleTitle
Human CD8+ CTL specific for the mycobacterial major secreted antigen 85A.
pubmed:affiliation
Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, United Kingdom. Steven.Smith@bristol.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't