Remodeling of the major mouse xenoantigen, Galalpha1-3Galbeta1-4GlcNAc-R, by N-acetylglucosaminyltransferase-III.
beta-D-Mannoside beta-1,4-N-acetylglucosaminyltransferase III (GnT-III) catalyses the attachment of an N-acetylglucosamine (GlcNAc) residue to mannose in the beta(1-4) configuration in N-glycans, and forms a bisecting GlcNAc. We have generated transgenic mice that contain the human GnT-III gene under the control of the mouse albumin enhancer/promoter [Lee et al., (2003)]. Overexpression of this gene in mice reduced the antigenicity of N-glycans to human natural antibodies, especially in the case of the alpha-Gal epitope, Galalpha1-3Galbeta1-4GlcNAc-R. Study of endothelial cells from the GnT-III transgenic mice revealed a significant reduction in antigenicity, and a dramatic decrease in both complement- and natural killer cell-mediated mouse cell lysis. Changes in the enzymatic activities of other glycosyltransferases, such as alpha1,3-galactosyltransferase, and alpha-6-D-mannoside beta-1,6 N-acetylglucosaminyltransferase V, did not point to any interaction between GnT-III and these enzymes in the transgenic mice, suggesting that this approach may be useful in clinical xenotransplantation.
Chung
Tae-Wook
TW
National Research Laboratory for Glycobiology, Korean Ministry of Science and Technology, Department of Biochemistry and Molecular Biology, Dongguk University COM, Kyungju 780-714, Korea.
Kim
Kyung-Sook
KS
Kang
Sung-Koo
SK
Lee
Jung-Woong
JW
Song
Eun-Young
EY
Chung
Tae-Hwa
TH
Yeom
Young-Il
YI
Kim
Cheorl-Ho
CH
D000818:Animals; D015478:Antigens, Heterophile / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D009844:Oligosaccharides / Q000276:immunology / Q000378:metabolism*
D015478:Antigens, Heterophile; D009844:Oligosaccharides; D017351:N-Acetylglucosaminyltransferases; C054599:beta-1,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase