Immunogenic Gal alpha 1----3Gal carbohydrate epitopes are present on pathogenic American Trypanosoma and Leishmania.
Anti-Gal is a natural antibody present in unusually high concentrations in human sera. It constitutes as much as 1% of circulating IgG and displays a distinct specificity for the Gal alpha 1----3Gal carbohydrate epitope. In the present study, we have found in the sera of patients with Chagas' disease and Leishmania infection anti-Gal titers 10- and 16-fold higher than that of healthy or bacteria-infected individuals. This increase in anti-Gal titer seemed to be the result of a specific immune response toward parasitic Gal alpha 1----3Gal epitopes. Binding studies of affinity chromatography-purified anti-Gal antibodies to Trypanosoma cruzi and American Leishmania parasites indeed demonstrated the presence of Gal alpha 1----3Gal epitopes on these parasites. This finding was supported by the observed binding to the parasites of two additional Gal alpha 1----3Gal recognizing molecules: the mAb Gal-13, and the lectin, Bandeiraea simplicifolia I B4. Furthermore, the binding of both anti-Gal antibody and of the B. simplicifolia I B4 lectin could be inhibited by galactose, and not glucose. In addition, removal of the terminal alpha-galactosyl residues from the parasites by pretreatment with alpha-galactosidase, or the oxidation of the binding epitopes by periodate prevented the subsequent binding of both the antibody and the lectin. A crude leishmanial lipid extract readily bound these three reagents, suggesting that at least part of these epitopes are of a glycolipid nature. These Gal alpha 1----3Gal epitopes may thus serve as an antigenic source for the excess production of anti-Gal. In view of the naturally high level of anti-Gal in humans and its binding to T. cruzi and Leishmania, it is argued that these antibodies may contribute to the natural defense against the invasion of such parasites.
Avila
J L
JL
Instituto de Biomedicina, Caracas, Venezuela.
Rojas
M
M
Galili
U
U
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000913:Antibodies, Protozoan / Q000032:analysis; D000939:Epitopes / Q000032:analysis*; D005690:Galactose / Q000276:immunology*; D006017:Glycolipids / Q000032:analysis; D006801:Humans; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000032:analysis; D037102:Lectins / Q000378:metabolism; D007891:Leishmania / Q000276:immunology*; D037121:Plant Lectins; D014349:Trypanosoma cruzi / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D000939:Epitopes; D006017:Glycolipids; C045475:Griffonia simplicifolia lectins; D007074:Immunoglobulin G; D037102:Lectins; D037121:Plant Lectins; D005690:Galactose