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Peptide-based analysis of the amino acid sequence important to the immunoregulatory function of Trypanosoma cruzi Tc52 virulence factor
- Source :
- Immunology. 109:147-155
- Publication Year :
- 2003
- Publisher :
- Wiley, 2003.
-
Abstract
- 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 micro g/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.
- Subjects :
- Male
Ovalbumin
Trypanosoma cruzi
Immunology
Protozoan Proteins
Down-Regulation
Virulence
Peptide
Biology
Lymphocyte Activation
Epitope
Conserved sequence
Interferon-gamma
Mice
Immune Tolerance
Animals
Immunology and Allergy
Amino Acid Sequence
Peptide sequence
chemistry.chemical_classification
Mice, Inbred BALB C
Original Articles
biology.organism_classification
Molecular biology
Peptide Fragments
Amino acid
Biochemistry
chemistry
Mice, Inbred CBA
biology.protein
Cytokines
Interleukin-2
Lymph Nodes
Cell Division
Spleen
Subjects
Details
- ISSN :
- 13652567 and 00192805
- Volume :
- 109
- Database :
- OpenAIRE
- Journal :
- Immunology
- Accession number :
- edsair.doi.dedup.....b6013bee7c9da987183281a40509a857