Target cell susceptibility to lysis by human natural killer cells is augmented by alpha(1,3)-galactosyltransferase and reduced by alpha(1, 2)-fucosyltransferase

Susceptibility of porcine endothelial cells to human natural killer (NK) cell lysis was found to reflect surface expression of ligands containing Gal alpha(1,3)Gal beta(1,4)GlcNAc [corrected], the principal antigen on porcine endothelium recognized by xenoreactive human antibodies. Genetically modif...

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Bibliographic Details
Published in:The Journal of biological chemistry 1999-04, Vol.274 (16), p.10717-10722
Main Authors: Artrip, J H, Kwiatkowski, P, Michler, R E, Wang, S F, Tugulea, S, Ankersmit, J, Chisholm, L, McKenzie, I F, Sandrin, M S, Itescu, S
Format: Article
Language:English
Subjects:
Animals
Cells, Cultured
COS Cells
Endothelium, Vascular - cytology
Endothelium, Vascular - immunology
Fucosyltransferases - metabolism
Galactosyltransferases - metabolism
Humans
Killer Cells, Natural - immunology
Swine
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Summary:Susceptibility of porcine endothelial cells to human natural killer (NK) cell lysis was found to reflect surface expression of ligands containing Gal alpha(1,3)Gal beta(1,4)GlcNAc [corrected], the principal antigen on porcine endothelium recognized by xenoreactive human antibodies. Genetically modifying expression of this epitope on porcine endothelium by transfection with the alpha(1,2)-fucosyltransferase gene reduced susceptibility to human NK lysis. These results indicate that surface carbohydrate remodeling profoundly affects target cell susceptibility to NK lysis, and suggest that successful transgenic strategies to limit xenograft rejection by NK cells and xenoreactive antibodies will need to incorporate carbohydrate remodeling.
ISSN:0021-9258
DOI:10.1074/jbc.274.16.10717