Human preformed IgG combining with membrane-bound porcine serotransferrin lyse porcine endothelial cells through antibody-dependent cellular cytotoxicity.
Preformed antibodies are involved in xenograft rejection. The purpose of this work was to characterize porcine xenoantigens recognized by human preformed IgG (hpIgG), and to investigate the role of hpIgG in xenogeneic rejection. IgG eluted from porcine livers perfused with human plasma, human sera and total human IgG were immunoblotted on porcine aortic endothelial cell extracts. The amino acid sequence of a 76-kDa antigen constantly revealed was 100% homologous with porcine serotransferrin (psTf). hpIgG from human sera, human IgG1 and IgG2 and F(ab')2gamma specifically bound to psTf. Neutralization by psTf abolished that binding. Although alpha1,3-linked galactose residues (Gal(alpha)1,3Gal) is the dominant epitope recognized by preformed antibodies in the swine-to-human combination, the analysis of carbohydrate composition of psTf showed that the molecule was devoid of Gal(alpha)1,3Gal moieties and that preformed anti-psTf IgG bound to epitopes localized on the peptide core of the molecule. Purified human anti-psTf IgG antibodies were able to bind to psTf linked to its receptor on porcine endothelial cells, and to kill those cells through antibody-dependent cellular cytotoxicity.
Atia
N
N
Laboratoire d'Immunologie, Faculté Cochin, Université Paris V, France.
Camoin
L
L
Duflos
G
G
Malassagne
B
B
Chéreau
C
C
Filipponi
F
F
Mahboub
S
S
Batteux
F
F
Conti
F
F
Michalski
J C
JC
Houssin
D
D
Calmus
Y
Y
Weill
B
B
D000595:Amino Acid Sequence; D000818:Animals; D000910:Antibodies, Heterophile / Q000276:immunology*; D015478:Antigens, Heterophile / Q000235:genetics / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000276:immunology; D013552:Swine; D014168:Transferrin / Q000276:immunology*
D000910:Antibodies, Heterophile; D015478:Antigens, Heterophile; D007074:Immunoglobulin G; D010455:Peptides; D014168:Transferrin