Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/10427
Title: Carbohydrate residues downstream of the terminal Galalpha(1,3)Gal epitope modulate the specificity of xenoreactive antibodies.
Authors: Milland, Julie;Yuriev, Elizabeth;Xing, Pei-Xiang;McKenzie, Ian F C;Ramsland, Paul A;Sandrin, Mauro S
Affiliation: Department of Surgery (Austin Health), University of Melbourne, Heidelberg, Victoria, Australia.
Issue Date: 28-Aug-2007
Citation: Immunology and Cell Biology 2007; 85(8): 623-32
Abstract: Carbohydrates are involved in many immunological responses including the rejection of incompatible blood, tissues and organs. Carbohydrate antigens with Galalpha(1,3)Gal epitopes are recognized by natural antibodies in humans and pose a major barrier for pig-to-human xenotransplantation. Genetically modified pigs have been established that have no functional alpha1,3-galactosyltransferase (alpha1,3GT), which transfers alphaGal to N-acetyllactosamine (LacNAc) type oligosaccharides. However, a low level of Galalpha(1,3)Gal is still expressed in alpha1,3GT knockout animals in the form of a lipid, isoglobotrihexosylceramide (iGb3), which is produced by iGb3 synthase on lactose (Lac) type core structures. Here, we define the reactivity of a series of monoclonal antibodies (mAb) generated in alpha1,3GT-/- mice immunized with rabbit red blood cells (RbRBC), as a rich source of lipid-linked antigens. Interestingly, one mAb (15.101) binds weakly to synthetic and cell surface-expressed Galalpha(1,3)Gal on LacNAc, but strongly to versions of the antigen on Lac cores, including iGb3. Three-dimensional models suggest that the terminal alpha-linked Gal binds tightly into the antibody-binding cavity. Furthermore, antibody interactions were predicted with the second and third monosaccharide units. Collectively, our findings suggest that although the terminal carbohydrate residues confer most of the binding affinity, the fine specificity is determined by subsequent residues in the oligosaccharide.
Internal ID Number: 17724458
URI: http://ahro.austin.org.au/austinjspui/handle/1/10427
DOI: 10.1038/sj.icb.7100111
URL: http://www.ncbi.nlm.nih.gov/pubmed/17724458
Type: Journal Article
Subjects: Animals
Antibodies, Heterophile.immunology
Antibodies, Monoclonal.immunology
Antibody Affinity
Antibody Specificity.immunology
Antigens.immunology
Binding Sites, Antibody
Carbohydrates.immunology
Cell Line
Disaccharides.immunology
Enzyme-Linked Immunosorbent Assay
Epitopes.immunology
Glycoconjugates.immunology
Humans
Hydrogen Bonding
Mice
Models, Molecular
Oligosaccharides.immunology
Appears in Collections:Journal articles

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