Complement-mediated lysis of Trypanosoma cruzi trypomastigotes by human anti-alpha-galactosyl antibodies.
Antibodies that lyse trypomastigotes in a complement-mediated reaction are believed to be the main participants in the protection against virulent Trypanosoma cruzi. Antibodies with a specificity for alpha-galactosyl-containing determinants--generally called antiGal--were studied to determine their role in the lysis of trypomastigote forms. The titers of antiGal markedly increase in Chagas's disease. In the present study we demonstrate binding of this antibody to T. cruzi and the complement-mediated lysis of trypomastigotes by antiGal. Lysis of metacyclic trypomastigotes by whole Chagasic (Ch) serum or isolated antiGal fractions was equally inhibited by alpha- but not by beta-galactosides. Most of the lytic power of the Ch antiGal as well as of the whole Ch serum was removed by absorption on Synsorb-linked Gal alpha 1, 3Gal beta 1, 4GlcNAc followed by rabbit erythrocyte absorption. The Ch antiGal had a lower affinity for melibiose bound to agarose than for the trisaccharide linked to Synsorb, and was several times more effective in the immunolysis of trypomastigotes than the corresponding antiGal from normal human serum. Lytic antibodies were partly absorbed by Serratia marcescens but not by Escherichia coli O111. A human volunteer immunized with an S. marcescens vaccine elicited a specific antiGal response that was lytic to trypomastigotes (70% lysis). We suggest that in vivo high-affinity antiGal antibody clones, as occur in Ch patients, may significantly contribute to the destruction of the parasite, whereas low-affinity antiGal clones are much less effective in the protection against T. cruzi infection.
Almeida
I C
IC
Disciplina de Biologia Celular, Escola Paulista de Medicina, São Paulo, Brazil.
Milani
S R
SR
Gorin
P A
PA
Travassos
L R
LR
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D000915:Antibody Affinity; D000918:Antibody Specificity; D000942:Antigens, Bacterial / Q000276:immunology; D002240:Carbohydrate Sequence; D014355:Chagas Disease / Q000276:immunology*; D003167:Complement Activation; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D005697:Galactosides / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D012706:Serratia marcescens / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology*
D000913:Antibodies, Protozoan; D000942:Antigens, Bacterial; D000939:Epitopes; D005697:Galactosides