Mycobacterium tuberculosis epitope-specific interferon-g production in healthy Brazilians reactive and non-reactive to tuberculin skin test

2018-08-162018-08-162014-12SILVA, Bosco Christiano Maciel da; GRASSI, Maria Fernanda Rios; COUTINHO, Raimundo; MASCARENHAS, Rita Elizabeth Moreira; OLAVARRIA, Viviana Nilla; COUTINHO-BORGO, Adriana; KALIL, Jorge; CUNHA-NETO, Edecio; FONSECA, Simone Gonçalves. Mycobacterium tuberculosis epitope-specific interferon-g production in healthy Brazilians reactive and non-reactive to tuberculin skin test. Memórias do Instituto Oswaldo Cruz, Rio de Janeiro, v. 109, n. 8, p. 999-1004, Dec. 2014.0074-0276e- 1678-8060http://repositorio.bc.ufg.br/handle/ri/15614The interferon (IFN)-γ 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-γ 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-γ production by PBMCs from at least 31% of the TST-positive donors. The magnitude of the response against all pep- tides was 182 ± 230 x 10 6 IFN-γ 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-γ assays to identify individuals with this condition.engAcesso AbertoMycobacterium tuberculosisMantoux tuberculin skin testEpitopesIFN-γ ELISPOTLatent tuberculosisMycobacterium tuberculosis epitope-specific interferon-g production in healthy Brazilians reactive and non-reactive to tuberculin skin testArtigo10.1590/0074-0276140193