Mycobacterium tuberculosis epitope-specific interferon-gamma production in healthy Brazilians reactive and non-reactive to tuberculin skin test
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2014-12-01
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Maciel da Silva, Bosco Christiano 
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The interferon (IFN)-gamma response to peptides can be a useful diagnostic marker of Mycobacterium tuberculosis (MTB) latent infection. We identified promiscuous and potentially protective CD4(+) T-cell epitopes from the most conserved regions of MTB antigenic proteins by scanning the MTB antigenic proteins GroEL2, phosphate-binding protein 1 precursor and 19 kDa antigen with the TEPITOPE algorithm. Seven peptide sequences predicted to bind to multiple human leukocyte antigen (HLA)-DR molecules were synthesised and tested with IFN-gamma enzyme-linked immunospot (ELISPOT) assays using peripheral blood mononuclear cells (PBMCs) from 16 Mantoux tuberculin skin test (TST)-positive and 16 TST-negative healthy donors. Eighty-eight percent of TST-positive donors responded to at least one of the peptides, compared to 25% of TST-negative donors. Each individual peptide induced IFN-gamma production by PBMCs from at least 31% of the TST-positive donors. the magnitude of the response against all peptides was 182 +/- 230 x 10(6) IFN-gamma spot forming cells (SFC) among TST-positive donors and 36 +/- 62 x 10(6) SFC among TST-negative donors (p = 0.007). the response to GroEL2 (463-477) was only observed in the TST-positive group. This combination of novel MTB CD4 T-cell epitopes should be tested in a larger cohort of individuals with latent tuberculosis (TB) to evaluate its potential to diagnose latent TB and it may be included in ELISPOT-based IFN-gamma assays to identify individuals with this condition.
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Memorias Do Instituto Oswaldo Cruz. Rio de Janeiro, Rj: Fundaco Oswaldo Cruz, v. 109, n. 8, p. 999-1004, 2014.