title: Modulation of the in vivo primate anti-Gal response through administration of anti-idiotypic antibodies.
abstract: Polyclonal anti-idiotypic antibodies (AIA) were generated against human Gal alpha 1,3Gal antibodies (anti-Gal) isolated from a single donor. Specificity of the AIA was demonstrated by selective binding to anti-Gal antibodies (Ab) and absence of reactivity to non-Gal Ab. The idiotopes identified by AIA were present on anti-Gal Ab from all of the human samples evaluated (n=59) as well as on pooled samples, demonstrating that a restricted number of dominant idiotopes characterized the human anti-Gal Ab response. Furthermore, the AIA had cross-species reactivity with baboon serum samples (n=19), suggesting that the overall shape of the anti-Gal Ab combining site is conserved throughout the Old World primates and providing additional evidence of the limited heterogeneity of the anti-Gal Ab repertoire. In order to evaluate the potential effect of AIA in the modulation of the anti-Gal response in vivo, a baboon was injected with repeated doses of the purified AIA. Following AIA treatment, new Ab were generated that reduced Ab-mediated cytotoxicity to porcine cells. Furthermore, administration of the AIA to a baboon prolonged the survival of intravenously infused pig hematopoietic cells when compared with their survival in a control baboon that did not receive prior AIA treatment but underwent a similar conditioning regimen.
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston 02129, USA. isabel.mcmorrow@tbrc.mgh.harvard.edu
authors.forename: Isabel M
authors.initials: IM
authors.lastname: McMorrow
authors.forename: Leo
authors.initials: L
authors.lastname: Buhler
authors.forename: Sarah
authors.initials: S
authors.lastname: Treter
authors.forename: Francisca A
authors.initials: FA
authors.lastname: Neethling
authors.forename: Ian P J
authors.initials: IP
authors.lastname: Alwayn
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Comrack
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitamura
authors.forename: Michel
authors.initials: M
authors.lastname: Awwad
authors.forename: Harout
authors.initials: H
authors.lastname: DerSimonian
authors.forename: David K C
authors.initials: DK
authors.lastname: Cooper
authors.forename: David H
authors.initials: DH
authors.lastname: Sachs
authors.forename: Christian
authors.initials: C
authors.lastname: LeGuern
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage* / Q000276:immunology; D004187:Disaccharides / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D010215:Papio; D013552:Swine; D013556:Swine, Miniature; D014181:Transplantation Immunology; D014183:Transplantation, Heterologous
chemical_list: D000888:Antibodies, Anti-Idiotypic; D004187:Disaccharides; C055075:galactosyl-(1-3)galactose