T Cell Responses to a Mixture of Mycobacterium Tuberculosis Peptides With Complementary HLA-DR Binding Profiles

Clin Exp Immunol. 1996 Sep;105(3):416-21. doi: 10.1046/j.1365-2249.1996.d01-791.x.

Abstract

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.

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Bacterial Proteins / immunology*
  • Bacterial Proteins / metabolism*
  • Female
  • HLA-DR Antigens / metabolism*
  • Humans
  • Interferon-gamma / biosynthesis
  • Lymphocyte Activation / drug effects*
  • Male
  • Molecular Sequence Data
  • Mycobacterium tuberculosis / immunology*
  • Peptides / immunology*
  • Peptides / metabolism*
  • T-Lymphocytes / immunology*

Substances

  • Bacterial Proteins
  • HLA-DR Antigens
  • Peptides
  • Interferon-gamma