title: Glycosylphosphatidylinositol-anchored mucin-like glycoproteins from Trypanosoma cruzi bind to CD1d but do not elicit dominant innate or adaptive immune responses via the CD1d/NKT cell pathway.
abstract: It has been proposed that self and protozoan-derived GPI anchors are natural ligands of CD1d. In this study, we investigated the ability of GPI anchors from Trypanosoma cruzi to bind to CD1d and mediate activation of NKT cells. We observed that GPI-anchored mucin-like glycoproteins (GPI mucins), glycoinositolphospholipids (GIPLs), and their phosphatidylinositol moieties bind to rCD1d and inhibit the stimulation of a NKT hybridoma by the alpha-galactosylceramide-CD1 complex. However, these GPI anchors and related structures were unable to activate NKT cells in vitro or in vivo. We found that high titers of Ab anti-GPI mucins, but not anti-GIPLs, were detected in sera from wild-type as well as in TAP1(-/-), CD1d(-/-), and MHC class II(-/-) mice after immunization. However, T-dependent anti-GPI mucin Ab isotypes, such as IgG1, IgG2a, IgG2b, and IgG3, were absent on MHC class II(-/-), but were conserved in CD1d(-/-) and TAP1(-/-) mice. Furthermore, we found that CD1d(-/-) mice presented a robust cytokine as well as anti-GPI mucins and anti-GIPL Ab responses, upon infection with T. cruzi parasites. These results indicate that, despite binding to CD1d, GPI mucins and related structures expressed by T. cruzi appear not to evoke dominant CD1d-restricted immune responses in vivo. In contrast, MHC class II is critical for the production of the major Ig G isotypes against GPI mucins from T. cruzi parasites.
authors.affiliation: Department of Biochemistry and Immunology and School of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Daniela O
authors.initials: DO
authors.lastname: Procópio
authors.forename: Igor C
authors.initials: IC
authors.lastname: Almeida
authors.forename: Ana Cláudia T
authors.initials: AC
authors.lastname: Torrecilhas
authors.forename: Jarbas E
authors.initials: JE
authors.lastname: Cardoso
authors.forename: Luc
authors.initials: L
authors.lastname: Teyton
authors.forename: Luiz R
authors.initials: LR
authors.lastname: Travassos
authors.forename: Albert
authors.initials: A
authors.lastname: Bendelac
authors.forename: Ricardo T
authors.initials: RT
authors.lastname: Gazzinelli
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis / Q000097:blood; D018949:Antigens, CD1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D055610:Antigens, CD1d; D001667:Binding, Competitive / Q000276:immunology; D002240:Carbohydrate Sequence; D002478:Cells, Cultured; D014355:Chagas Disease / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins / Q000378:metabolism* / Q000502:physiology; D017261:Glycosylphosphatidylinositols / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D007113:Immunity, Innate / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D008262:Macrophage Activation / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009077:Mucins / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D015800:Protozoan Proteins / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D014349:Trypanosoma cruzi / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
chemical_list: D000913:Antibodies, Protozoan; D018949:Antigens, CD1; D055610:Antigens, CD1d; D016207:Cytokines; D006023:Glycoproteins; D017261:Glycosylphosphatidylinositols; D009077:Mucins; D015800:Protozoan Proteins