Abstract
The major barrier to transplantation across discordant species, such as from pig to human, is rejection mediated by xenoreactive natural antibodies (XNA) that bind the carbohydrate epitope Galalpha1-3Galbeta1-4GlcNAc-R (alphaGal) on donor tissues. This epitope is synthesized by the enzyme glucosyltransferase uridine 5'-diphosphate galactose:beta-D-galactosyl-1, 4-N-acetyl-D-glucosaminide alpha(1-3)galactosyltransferase (E.C. 2.4.1.151), or simply alphaGT. When a functional alphaGT gene was introduced by retroviral gene transfer into bone marrow cells, alphaGal XNA production in a murine model ceased. Thus, genetic engineering of bone marrow may overcome humoral rejection of discordant xenografts and may be useful for inducing B cell tolerance.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antibody Formation*
-
B-Lymphocytes / immunology
-
Bone Marrow Cells / enzymology*
-
Bone Marrow Transplantation
-
Cell Line
-
Cloning, Molecular
-
Enzyme-Linked Immunosorbent Assay
-
Epitopes / biosynthesis
-
Epitopes / immunology*
-
Galactosyltransferases / biosynthesis
-
Galactosyltransferases / genetics*
-
Galactosyltransferases / immunology*
-
Gene Targeting
-
Gene Transfer Techniques
-
Genetic Therapy*
-
Genetic Vectors
-
Graft Rejection / prevention & control*
-
Graft vs Host Disease / prevention & control
-
Humans
-
Immune Tolerance
-
Mice
-
Mice, Knockout
-
Retroviridae / genetics
-
Swine
-
Transplantation, Heterologous*
Substances
-
Epitopes
-
Galactosyltransferases
-
N-acetyllactosaminide alpha-1,3-galactosyltransferase