title: T-cell recognition of iron-regulated culture filtrate proteins of Mycobacterium tuberculosis in tuberculosis patients and endemic normal controls.
abstract: BACKGROUND
  Culture filtrate proteins (CFPs) of Mycobacterium tuberculosis are potential vaccine candidates.
  
  
  OBJECTIVE
  The aim was to study the influence of iron levels on CFPs and assess the immuno-protective potential of defined antigenic fractions from high (8 μg Fe/mL) and low iron (0.02 μg Fe / mL) cultures of M. tuberculosis.
  
  
  METHODS
  The CFPs of M. tuberculosis from high (CFP-high) and low (CFP-low) iron conditions were first compared to identify iron-regulated proteins and then fractionated to obtain ten antigen pools (CF-Ags H1- H5 and L1-L5) that were used to assess the immune response of TB patients and normal healthy controls.
  
  
  RESULTS
  Iron limitation resulted in the up-regulation of two novel iron-regulated low-molecular-weight proteins Irp-1 (in CF-Ag L4) and Irp-2 (in CF-Ag L5) and repression of two ESAT proteins (identified with monoclonal antibody HYB 76.8). The median stimulation indices (SIs) against most of the CF-Ags were high in pulmonary TB patients. The CF-Ags L1 and L2 showed statistically significant SI (P values of 0.0027 and 0.0029 respectively); the % case recognition was high with these antigens as well as with L4 ( P = 0.0275). IFN-γ in response to these CF-Ags was significantly high in the endemic normals; maximal expression was seen with CF-Ag L5 (median value of 233 pg mL -1 ) that was higher than the corresponding H5 (140 pg mL -1 ) and H3 and L3 (205 and 206 pg mL -1 respectively).
  
  
  CONCLUSIONS
  CF-Ags L5, H3 and L3 showed immuno-protective potential in this geographical location.
authors.affiliation: Department of Animal Sciences, University of Hyderabad, Andhra Pradesh, India.
authors.forename: S
authors.initials: S
authors.lastname: Duggirala
authors.forename: K
authors.initials: K
authors.lastname: Venu
authors.forename: K
authors.initials: K
authors.lastname: Subhakar
authors.forename: M
authors.initials: M
authors.lastname: Sritharan
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000096:biosynthesis / Q000276:immunology*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000276:immunology*; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007501:Iron