Articolo in rivista, 2009,

Design of immunogenic peptides from Mycobacterium tuberculosis genes expressed during macrophage infection

Seghrouchni F .a), Contini S. a), Markova R. c), Drenska R. c), Sadki K. b), Baassi L. b), Todorova Y. c), Terzieva V. c), Bocchino M. a), Cappelli G. d), Altieri A.M. e), Alma M.G. e), Benjouad A. f), Mariani F. d), Petrunov B. c), Colizzi V. g) et al.

a) Department of Internal Medicine, University of Rome “Tor Vergata”, Via Montpellier 1, 00133 Rome, Italy b) Laboratory of cellular immunology, Department of Immunology–Virology, National Institute of Hygiene, 27, Avenue Ibn Battouta, Agdal, P.B: 769, P.C.:11400 Rabat, Morocco c) Laboratory of Mediators of Inflammation and Immunity, Department of Immunology and Allergy, National Center of Infectious and Parasitic Diseases, Yanko Sakazov Boulevard 26, P.C.:1504 Sofia, Bulgaria d) Laboratory of Infectious Diseases, INMM-C.N.R., Area Ricerca “Tor Vergata”, Via del Fosso del Cavaliere 100, I-00133 Rome, Italy e) IV Medical Division of Respiratory Disease, “S. Camillo-Forlanini” Hospital, Circonvallazione Gianicolense, 87, P.C.:00152 Rome, Italy f) Laboratory of Biochemistry–Immunology, Department of Biology, University “Mohamed V-Agdal”, Av Ibn Battouta, P.C.: 10000, P.B.:1014 Rabat, Morocco g) Department of Biology, University of Rome “Tor Vergata”, Via della Ricerca Scientifica, 00133 Rome, Italy

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.

Tuberculosis (Edinb.) 89(3) , pp. 210–217

Keywords

Tuberculosis, Peptide-binding motifs, ELISpot, Macrophage-induced mycobacterial genes

CNR authors

Mariani Francesca, Cappelli Giulia

CNR institutes

INMM – Istituto di neurobiologia e medicina molecolare

ID: 4955

Year: 2009

Type: Articolo in rivista

Creation: 2010-01-27 00:00:00.000

Last update: 2012-06-22 18:20:44.000

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External IDs

CNR OAI-PMH: oai:it.cnr:prodotti:4955