T cell responses to a mixture of Mycobacterium tuberculosis peptides with complementary HLA-DR binding profiles.
The T cell response to a mixture of eight peptides derived from sequences of the Mycobacterium tuberculosis 16-, 19- and 38-kD antigens (MTBmix-8) has been studied. The peptides were selected on the basis of complementary binding to nine HLA-DR molecules (HLA-DR1 to DR9). MTBmix-8 at 6.25 and 50 micrograms/ml gave rise to significant stimulation (P < 0.05) of peripheral blood mononuclear cells (PBMC) from healthy tuberculin-positive and both untreated and treated diseased subjects, but not in any of a control group of healthy tuberculin-negative subjects. MTB-mix-8 stimulated proliferation of PBMC from healthy tuberculin-positive individuals at lower concentrations than the individual component peptides. However, the maximal stimulation achieved was only slightly higher than that achieved with individual peptides. MTBmix-8 also stimulated the production of interferon-gamma (IFN-gamma) in vitro. Using the mean +/- 2 s.d. of the values for IFN-gamma production in the tuberculin-negative population as a cut-off, MTBmix-8 at 6.25 micrograms/ml was able to detect infection with a sensitivity of 100% in untreated patients, 87% in treated patients, and 82% in tuberculin-positive controls. The corresponding figures for the most potent single peptide (16p91-110) were: 66% in untreated patients, 71% in treated patients and only 42% in controls. Thus, using the IFN-gamma-based assay, which has the additional advantages of speed and does not require radioactivity, the mixture of peptides is more sensitive than single peptides in diagnosing infection.
Jurcevic
S
S
Tuberculosis and Related Infections Unit, Hammersmith Hospital, London, UK.
Hills
A
A
Pasvol
G
G
Davidson
R N
RN
Ivanyi
J
J
Wilkinson
R J
RJ
D000328:Adult; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010455:Peptides / Q000276:immunology* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*
D001426:Bacterial Proteins; D006684:HLA-DR Antigens; D010455:Peptides; D007371:Interferon-gamma