Abstract
In vitro diagnosis of MTB-infection uses MTB-proteins coded for by genes of the region of differentiation 1 (RD1) of the MTB genome. This study wants to test if proteins preferentially expressed during MTB-intracellular growth might provide new targets for the diagnosis of MTB-infection. To this end seventy-five multiepitopic HLA-promiscuous MTB-peptides were designed by quantitative implemented peptide-binding motif analysis from 3 MTB-protein genes expressed in activated human macrophages (MA), 4 genes expressed during growth in non-activated human macrophages (MN-A), 12 housekeeping genes (HKG) and 6 genes of the RD1 region (RD1) as control. ELISpot for IFN-was performed to measure the responses of PBMCs deriving from 45 patients affected by active tuberculosis and 34 controls. In active-TB patients, the mean response to RD1-derived peptides was higher than that to either MA (p <0.01), MN-A (p <0.008) or HKG (p <0.01) derived peptides. In TST-positive subjects all selected peptides elicited significant IFN-T-cell responses (p <0.02 compared to TST-negatives), but without differences between the subgroups. Further, T-cell responses to RD1 peptides were lower in the 23 active-TB treated patients than in the untreated ones (p <0.01). The response to MA peptides in treated active-TB was higher than when untreated (p <0.01). These results demonstrate that the use of in vitro models of MTB-intracellular infection to select MTB gene products for further in silico and in vitro assessment of their immunogenicity have the potential to identify novel antigens amenable to the design of new tools for diagnosis and monitoring of tuberculosis.
| Original language | English |
|---|---|
| Pages (from-to) | 210-217 |
| Number of pages | 8 |
| Journal | Tuberculosis |
| Volume | 89 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - May 2009 |
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Keywords
- ELISpot
- Macrophage-induced mycobacterial genes
- Peptide-binding motifs
- Tuberculosis
ASJC Scopus subject areas
- Microbiology
- Immunology
- Infectious Diseases
- Microbiology (medical)
Cite this
Design of immunogenic peptides from Mycobacterium tuberculosis genes expressed during macrophage infection. / Seghrouchni, Fouad; Contini, Silvia; Markova, Roumiana; Drenska, Roumiana; Sadki, Khalid; Baassi, Larbii; Todorova, Yana; Terzieva, Velislava; Bocchino, Marialuisa; Cappelli, Giulia; Altieri, Alfonso Maria; Alma, Mario Giuseppe; Benjouad, Abdelaziz; Mariani, Francesca; Petrunov, Bogdan; Colizzi, Vittorio; El Aouad, Rajae; Saltini, Cesare; Amicosante, Massimo.
In: Tuberculosis, Vol. 89, No. 3, 05.2009, p. 210-217.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Design of immunogenic peptides from Mycobacterium tuberculosis genes expressed during macrophage infection
AU - Seghrouchni, Fouad
AU - Contini, Silvia
AU - Markova, Roumiana
AU - Drenska, Roumiana
AU - Sadki, Khalid
AU - Baassi, Larbii
AU - Todorova, Yana
AU - Terzieva, Velislava
AU - Bocchino, Marialuisa
AU - Cappelli, Giulia
AU - Altieri, Alfonso Maria
AU - Alma, Mario Giuseppe
AU - Benjouad, Abdelaziz
AU - Mariani, Francesca
AU - Petrunov, Bogdan
AU - Colizzi, Vittorio
AU - El Aouad, Rajae
AU - Saltini, Cesare
AU - Amicosante, Massimo
PY - 2009/5
Y1 - 2009/5
N2 - In vitro diagnosis of MTB-infection uses MTB-proteins coded for by genes of the region of differentiation 1 (RD1) of the MTB genome. This study wants to test if proteins preferentially expressed during MTB-intracellular growth might provide new targets for the diagnosis of MTB-infection. To this end seventy-five multiepitopic HLA-promiscuous MTB-peptides were designed by quantitative implemented peptide-binding motif analysis from 3 MTB-protein genes expressed in activated human macrophages (MA), 4 genes expressed during growth in non-activated human macrophages (MN-A), 12 housekeeping genes (HKG) and 6 genes of the RD1 region (RD1) as control. ELISpot for IFN-was performed to measure the responses of PBMCs deriving from 45 patients affected by active tuberculosis and 34 controls. In active-TB patients, the mean response to RD1-derived peptides was higher than that to either MA (p <0.01), MN-A (p <0.008) or HKG (p <0.01) derived peptides. In TST-positive subjects all selected peptides elicited significant IFN-T-cell responses (p <0.02 compared to TST-negatives), but without differences between the subgroups. Further, T-cell responses to RD1 peptides were lower in the 23 active-TB treated patients than in the untreated ones (p <0.01). The response to MA peptides in treated active-TB was higher than when untreated (p <0.01). These results demonstrate that the use of in vitro models of MTB-intracellular infection to select MTB gene products for further in silico and in vitro assessment of their immunogenicity have the potential to identify novel antigens amenable to the design of new tools for diagnosis and monitoring of tuberculosis.
AB - In vitro diagnosis of MTB-infection uses MTB-proteins coded for by genes of the region of differentiation 1 (RD1) of the MTB genome. This study wants to test if proteins preferentially expressed during MTB-intracellular growth might provide new targets for the diagnosis of MTB-infection. To this end seventy-five multiepitopic HLA-promiscuous MTB-peptides were designed by quantitative implemented peptide-binding motif analysis from 3 MTB-protein genes expressed in activated human macrophages (MA), 4 genes expressed during growth in non-activated human macrophages (MN-A), 12 housekeeping genes (HKG) and 6 genes of the RD1 region (RD1) as control. ELISpot for IFN-was performed to measure the responses of PBMCs deriving from 45 patients affected by active tuberculosis and 34 controls. In active-TB patients, the mean response to RD1-derived peptides was higher than that to either MA (p <0.01), MN-A (p <0.008) or HKG (p <0.01) derived peptides. In TST-positive subjects all selected peptides elicited significant IFN-T-cell responses (p <0.02 compared to TST-negatives), but without differences between the subgroups. Further, T-cell responses to RD1 peptides were lower in the 23 active-TB treated patients than in the untreated ones (p <0.01). The response to MA peptides in treated active-TB was higher than when untreated (p <0.01). These results demonstrate that the use of in vitro models of MTB-intracellular infection to select MTB gene products for further in silico and in vitro assessment of their immunogenicity have the potential to identify novel antigens amenable to the design of new tools for diagnosis and monitoring of tuberculosis.
KW - ELISpot
KW - Macrophage-induced mycobacterial genes
KW - Peptide-binding motifs
KW - Tuberculosis
UR - http://www.scopus.com/inward/record.url?scp=67349119048&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67349119048&partnerID=8YFLogxK
U2 - 10.1016/j.tube.2009.03.005
DO - 10.1016/j.tube.2009.03.005
M3 - Article
C2 - 19447677
AN - SCOPUS:67349119048
VL - 89
SP - 210
EP - 217
JO - Tuberculosis
JF - Tuberculosis
SN - 1472-9792
IS - 3
ER -