Retro-inverso peptide analogues of Trypanosoma cruzi B13 protein epitopes fail to be recognized by human sera and peripheral blood mononuclear cells

Retro-inverso peptide analogues of Trypanosoma cruzi B13 protein epitopes fail to be recognized by human sera and peripheral blood mononuclear cells

Author Iwai, L. K. Google Scholar
Duranti, M. A. Google Scholar
Abel, LCJ Google Scholar
Juliano, M. A. Google Scholar
Kalil, J. Google Scholar
Juliano, L. Google Scholar
Cunha-Neto, E. Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Abstract Retro inverso (RI) analogues of antigenic synthetic peptides, which are made of D-amino acids with a reversed sequence, may mimic the side chain conformation of natural all-L peptides. RI analogues were cross-reactively recognized by antibodies and CD4+ T cells reactive against natural all-L synthetic peptides or native proteins in animal models. Since peptides containing D-amino acids are highly resistant to proteolytic digestion, cross-reactive RI analogues may be ideal for in vivo administration to humans as synthetic peptide vaccines or immunomodulators. B13 is an immunodominant tandemly repetitive protein from Trypanosoma cruzi, a protozoan parasite that is the causative antigen of Chagas' disease. in order to test whether RI peptides can be recognized by human antibody and T cells, we synthesized two all-L peptides containing the immunodominant B (S12) and T (S15.7) cell epitopes of B13 protein from T. cruzi and their retro (R, made of all-L amino acids with reversed sequence), inverse (I, made of all-D amino acids) and RI analogues. Recognition of peptides S12, S12-R, S12-I and S12-RI by anti-B13 antibodies in sera from T. cruzi-infected patients was tested in competitive ELISA assay with recombinant B13 protein as the solid phase antigen. Peptides S15.7 and its topological analogues were tested at the 10-50 muM range in proliferation assays on peripheral blood mononuclear cells (PBMC) from S15.7-responder individuals. the median percentage inhibition of B13 ELISA for peptide S12 was 94%. while those of the RI analogue or the other topological analogues were below 12%. While peptide S15.7 was recognized by PBMC from all subjects tested, none recognized the RI analogue of the S15.7 T cell epitope. Our results indicate that cross-reactivity with natural epitopes is not an universal property of RI analogues. This may limit the general applicability of the use of cross-reactive RI analogues as human vaccines and immunotherapeutic agents. (C) 2001 Elsevier Science Inc. All rights reserved.
Language English
Date 2001-06-01
Published in Peptides. New York: Elsevier B.V., v. 22, n. 6, p. 853-860, 2001.
ISSN 0196-9781 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 853-860
Origin http://dx.doi.org/10.1016/S0196-9781(01)00409-0
Access rights Closed access
Type Article
Web of Science ID WOS:000169181800001
URI http://repositorio.unifesp.br/handle/11600/26571

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