Modulation of the in vivo primate anti-Gal response through administration of anti-idiotypic antibodies.
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.
McMorrow
Isabel M
IM
Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston 02129, USA. isabel.mcmorrow@tbrc.mgh.harvard.edu
Buhler
Leo
L
Treter
Sarah
S
Neethling
Francisca A
FA
Alwayn
Ian P J
IP
Comrack
Christopher A
CA
Kitamura
Hiroshi
H
Awwad
Michel
M
DerSimonian
Harout
H
Cooper
David K C
DK
Sachs
David H
DH
LeGuern
Christian
C
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
D000888:Antibodies, Anti-Idiotypic; D004187:Disaccharides; C055075:galactosyl-(1-3)galactose