title: The influence of natural antibody specificity on antigen immunogenicity.
abstract: The natural antibody repertoire in humans, apes and Old World primates is distinct from the repertoire of all other placental mammals, and encodes antibodies specific for the carbohydrate epitope Galalpha1-3Galbeta1-4GlcNAc-R (alphaGal). Here, we examined whether conjugating antigens to the alphaGal epitope can augment their immunogenicity in alpha(1,3)galactosyltransferase knockout mice (GT0 mice) which, like humans, produce alphaGal-specific antibodies. Immunization of GT0 mice with BSA conjugated to alphaGal (alphaGal-BSA) led to significant production of anti-BSA IgG antibodies without the need for adjuvant. This response was dependent on the presence of alphaGal-reactive antibodies. Immunization of wild-type mice with alphaGal-BSA failed to induce an anti-BSA response. The presence of alphaGal-reactive antibodies also led to an increase in the T cell response to BSA following immunization with alphaGal-BSA when compared with mice that received BSA alone, resulting in an increased frequency of IFN-gamma- and IL-4-producing BSA-specific T cells. In addition, the ability to produce alphaGal-reactive antibodies enhanced the cytotoxic T lymphocyte anti-viral antigen response following vaccination with murine leukemia virus transformed cell lines that express alphaGal on their cell surface. Natural antibodies that bind alphaGal therefore play a key role in increasing the efficiency of priming to antigens decorated with alphaGal epitopes.
authors.affiliation: Transplantation Research Center, Brigham and Women's Hospital and Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Benatuil
authors.forename: Joel
authors.initials: J
authors.lastname: Kaye
authors.forename: Robert F
authors.initials: RF
authors.lastname: Rich
authors.forename: Jay A
authors.initials: JA
authors.lastname: Fishman
authors.forename: William R
authors.initials: WR
authors.lastname: Green
authors.forename: John
authors.initials: J
authors.lastname: Iacomini
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D007114:Immunization; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011951:Receptors, Complement / Q000097:blood; D012710:Serum Albumin, Bovine / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014312:Trisaccharides / Q000276:immunology*
chemical_list: D000906:Antibodies; D011951:Receptors, Complement; D014312:Trisaccharides; C076569:alpha-galactosyl epitope; D015847:Interleukin-4; D012710:Serum Albumin, Bovine; D007371:Interferon-gamma