Please use this identifier to cite or link to this item:
Title: Carbohydrate residues downstream of the terminal Galalpha(1,3)Gal epitope modulate the specificity of xenoreactive antibodies.
Austin 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
Publication information: 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.
Gov't Doc #: 17724458
DOI: 10.1038/sj.icb.7100111
Journal: Immunology and cell biology
Type: Journal Article
Subjects: Animals
Antibodies, Heterophile.immunology
Antibodies, Monoclonal.immunology
Antibody Affinity
Antibody Specificity.immunology
Binding Sites, Antibody
Cell Line
Enzyme-Linked Immunosorbent Assay
Hydrogen Bonding
Models, Molecular
Appears in Collections:Journal articles

Show full item record

Page view(s)

checked on May 21, 2024

Google ScholarTM


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.