Peptide-based analysis of the amino acid sequence important to the immunoregulatory function of Trypanosoma cruzi Tc52 virulence factor

• Type: Article in International Scientific Journal
• Date: 2003

Authors

Borges, M (Author) FFUP; Da Silva, AC (Author) FFUP; Sereno, D (Author) Other; Ouaissi, A (Author) Other

Journal

Title: Immunology

Vol. 109

Pages: 147-155

ISSN: 0019-2805

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 24 Citations

Scopus - 24 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-000-GV2

DOI: 10.1046/j.1365-2567.2003.01637.x

Abstract (EN): The intracellular protozoan parasite Trypanosoma cruzi is the aetiological agent of Chagas' disease. We have previously identified a T. cruzi -released protein called Tc52, which is crucial for parasite survival and virulence. In the present study, we attempted to define the Tc52 epitope(s) responsible for its immunoregulatory function. A naturally occurring major peptide fragment of molecular mass 28 kDa (Tc28k) was identified, which was localized in the C-terminal portion of Tc52 and was inhibitory for T-cell activation. Synthetic peptides corresponding to amino acid sequences in Tc52 were evaluated for their ability to modulate T-cell proliferation and cytokine production. Results obtained using five peptides spanning the N-terminal or C-terminal domain of the Tc52 protein indicated that the activity mapped to Tc52 residues 432-445. Moreover, it was found that the peptide, when coupled to a carrier protein (ovalbumin), exhibited increased inhibitory activity on T-lymphocyte activation. Incubation with 8 nm ovalbumin-coupled peptide 432-445 resulted in approximately the same levels (>75%) of inhibition of T-cell proliferation as 5 mug/ml Tc28k. Furthermore, we showed that the coupled peptide significantly down-regulated the secretion of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2). Likewise, in immunized mice, the coupled peptide 432-445 was a very poor B- and T-cell antigen compared with the other Tc52-derived peptides. These results suggest that the immunomodulatory portion of the T. cruzi Tc52 virulent factor may reside, at least in part, in a conserved sequence within its C-terminal domain, which could minimize its antigenicity.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9