Antibody responses to the fucosylated LacdiNAc glycan antigen in Schistosoma mansoni-infected mice and expression of the glycan among schistosomes.
Infections of animals with parasitic worms, such as Schistosoma mansoni, induce humoral immune responses to carbohydrate antigens, raising the possibility that such antigens might be useful targets for the development of vaccines and new diagnostic approaches. Here we describe the identification of fucosylated LacdiNAc (LDNF) [GalNAc beta 1-4(Fuc alpha 1-3)GlcNAc-R] as a new carbohydrate antigen in S. mansoni that induces humoral immune responses in infected mice. The presence of antibodies was determined by ELISA using a neoglycoconjugate synthesized to express LDNF sequences. Sera from S. mansoni-infected, but not uninfected, mice contain IgM, IgG, IgA, and IgE antibodies to LDNF. The IgG antibodies are primarily of the IgG1 and IgG3 subclasses, with no detectable levels of the complement-fixing IgG2a and IgG2b isotypes. An IgM monoclonal antibody, designated SMLDNF1, was generated from the spleens of S. mansoni-infected mice, and the antibody exhibits specific recognition of LDNF sequences, but not other fucosylated glycans tested. Immunocytochemical analysis demonstrates that LDNF antigens are localized on the tegumental surface of adult S. mansoni. Western blot analysis indicates that LDNF sequences are expressed on numerous high-molecular-weight glycoproteins from the three major human schistosome species, as well as the bird schistosome Trichobilharzia ocellata. The identification of LDNF antigen on the tegumental glycoproteins of schistosomes and the ability to synthesize LDNF conjugates should aid in the development of glycan-based vaccines and immunodiagnostic tests for schistosomiasis and in determining the role(s) of the glycans in worm development and pathogenesis.
Nyame
A K
AK
Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Biomedical Research Center, Room 417, 975 NW 10th Street, Oklahoma City, Oklahoma 73104, USA.
Leppänen
A M
AM
Bogitsh
B J
BJ
Cummings
R D
RD
D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis* / Q000097:blood / Q000145:classification; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D000947:Antigens, Helminth / Q000737:chemistry / Q000276:immunology*; D015153:Blotting, Western; D002240:Carbohydrate Sequence; D004187:Disaccharides / Q000737:chemistry / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000737:chemistry / Q000276:immunology; D006801:Humans; D006825:Hybridomas; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D007150:Immunohistochemistry; D007785:Lactose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000737:chemistry / Q000276:immunology; D012550:Schistosoma mansoni / Q000276:immunology* / Q000378:metabolism; D012555:Schistosomiasis mansoni / Q000276:immunology*
D000909:Antibodies, Helminth; D000911:Antibodies, Monoclonal; D000947:Antigens, Helminth; D004187:Disaccharides; D006023:Glycoproteins; D007074:Immunoglobulin G; D011134:Polysaccharides; C093701:N-acetylgalactosaminyl-1-4-N-acetylglucosamine; D007785:Lactose