Skjøt, Rikke Louise Vinther;
Oettinger, Thomas;
Rosenkrands, Ida;
Ravn, Pernille;
Brock, Inger;
Jacobsen, Susanne;
Andersen, Peter
Comparative Evaluation of Low-Molecular-Mass Proteins fromMycobacterium tuberculosisIdentifies Members of the ESAT-6 Family as Immunodominant T-Cell Antigens
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Medientyp:
E-Artikel
Titel:
Comparative Evaluation of Low-Molecular-Mass Proteins fromMycobacterium tuberculosisIdentifies Members of the ESAT-6 Family as Immunodominant T-Cell Antigens
Beteiligte:
Skjøt, Rikke Louise Vinther;
Oettinger, Thomas;
Rosenkrands, Ida;
Ravn, Pernille;
Brock, Inger;
Jacobsen, Susanne;
Andersen, Peter
Erschienen:
American Society for Microbiology, 2000
Erschienen in:
Infection and Immunity, 68 (2000) 1, Seite 214-220
Sprache:
Englisch
DOI:
10.1128/iai.68.1.214-220.2000
ISSN:
0019-9567;
1098-5522
Entstehung:
Anmerkungen:
Beschreibung:
ABSTRACTCulture filtrate fromMycobacterium tuberculosiscontains protective antigens of relevance for the generation of a new antituberculosis vaccine. We have identified two previously uncharacterizedM. tuberculosisproteins (TB7.3 and TB10.4) from the highly active low-mass fraction of culture filtrate. The molecules were characterized, mapped in a two-dimensional electrophoresis reference map of short-term culture filtrate, and compared with another recently identified low-mass protein, CFP10 (F. X. Berthet, P. B. Rasmussen, I. Rosenkrands, P. Andersen, and B. Gicquel. Microbiology 144:3195–3203, 1998), and the well-described ESAT-6 antigen. Genetic analyses demonstrated that TB10.4 as well as CFP10 belongs to the ESAT-6 family of low-mass proteins, whereas TB7.3 is a low-molecular-mass protein outside this family. The proteins were expressed inEscherichia coli, and their immunogenicity was tested in cultures of peripheral blood mononuclear cells from human tuberculosis (TB) patients,Mycobacterium bovisBCG-vaccinated donors, and nonvaccinated donors. The two ESAT-6 family members, TB10.4 and CFP10, were very strongly recognized and induced gamma interferon release at the same level (CFP10) as or at an even higher level (TB10.4) than ESAT-6. The non-ESAT-6 family member, TB7.3, for comparison, was recognized at a much lower level. CFP10 was found to distinguish TB patients from BCG-vaccinated donors and is, together with ESAT-6, an interesting candidate for the diagnosis of TB. The striking immunodominance of antigens within the ESAT-6 family is discussed, and hypotheses are presented to explain this targeting of the immune response during TB infection.