Trypanosoma cruzi: conformational preferences of antigenic peptides bearing the immunodominant epitope of the B13 antigen.
The Trypanosoma cruzi recombinant protein B13 contains tandemly repeated domains and shows high sensitivity in the serological diagnosis of Chagas' disease. It has been shown that the immunodominant epitope of B13 is contained in the GDKPSLFGQAAAGDKPSLF-NH(2) sequence and that the hexapeptide AAAGDK seems to be the "core" of that epitope. Three peptides containing that "core" sequence, one corresponding to the entire repeat motif GDKPSLFGQAAAGDKPSLF-NH(2), pB13, and two smaller fragments, FGQAAAGDK-NH(2), S4, and QAAAGDKPS-NH(2), S5, have been tested in competitive ELISA with recombinant protein B13 in the solid phase against 40 chagasic sera from Brazilian patients. The median percentage inhibition for pB13, S4, and S5 were, respectively, 91, 86, and 68%. The possibility that the distinct antigenic activity of those peptides correlates with the existence of preferential conformational properties has been investigated by CD and NMR spectroscopy. Results indicate their propensity to adopt a helical configuration, centered in the AAAGDK sequence, and whose extent and stability directly correlates with the peptides' antigenicity. The data are discussed in the light of the existence of conformational preferences involving immunodominant epitopes in tandemly repeated antigens.
Duranti
M A
MA
Laboratory of Transplantation Immunology, Heart Institute, Faculty of Medicine, University of São Paulo, SP, Brazil.
Franzoni
L
L
Sartor
G
G
Benedetti
A
A
Iwai
L K
LK
Gruber
A
A
Zingales
B
B
Guzman
F
F
Kalil
J
J
Spisni
A
A
Cunha-Neto
E
E
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry* / Q000276:immunology; D014355:Chagas Disease / Q000276:immunology*; D002942:Circular Dichroism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry* / Q000276:immunology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D020080:Tandem Repeat Sequences / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology*
D000953:Antigens, Protozoan; D016056:Immunodominant Epitopes