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

Memórias do Instituto Oswaldo Cruz

Bosco Christiano Maciel Da Silva¹  Maria Fernanda Rios Grassi¹  Raimundo Coutinho¹  Rita Elizabeth Moreira Mascarenhas¹  Viviana Nilla Olavarria¹  Adriana Coutinho-borgo¹  Jorge Kalil¹  Edecio Cunha Neto¹  Simone Gonçalves Fonseca¹ 

关键词: Mycobacterium tuberculosis;    epitopes;    IFN-γ ELISPOT;    latent tuberculosis;    Mantoux tuberculin skin test;   

DOI  :  10.1590/0074-0276140193

来源: SciELO

【 摘 要 】

The 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 peptides was 182 ± 230 x 106 IFN-γ spot forming cells (SFC) among TST-positive donors and 36 ± 62 x 106 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.

【 授权许可】

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