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Identification of New Carbohydrate and Membrane Protein Antigens in Cardiac Xenotransplantation

Byrne, GW; Stalboerger, PG; Du, ZJ; Davis, TR; McGregor, CGA; (2011) Identification of New Carbohydrate and Membrane Protein Antigens in Cardiac Xenotransplantation. TRANSPLANTATION , 91 (3) 287 - 292. 10.1097/TP.0b013e318203c27d.

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Abstract

Background. alpha 1,3-Galactosyltransferase gene knockout (GTKO) pigs reduced the significance of antibody to galactose alpha 1,3-galactose (Gal) antigens but did not eliminate delayed xenograft rejection (DXR). We hypothesize that DXR of GTKO organs results from an antibody response to a limited number of non-Gal endothelial cell (EC) membrane antigens. In this study, we screened a retrovirus expression library to identify EC membrane antigens detected after cardiac xenotransplantation.Methods. Expression libraries were made from GT(+):CD46 and GTKO porcine aortic ECs. Viral stocks were used to infect human embryonic kidney cells (HEK) that were selected by flow cytometry for IgG binding from sensitized cardiac heterotopic xenograft recipients. After three to seven rounds of selection, individual clones were assessed for non-Gal IgG binding. The porcine complementary DNA was recovered by polymerase chain reaction amplification, sequenced, and identified by homology comparisons.Results. A total of 199 and 317 clones were analyzed from GT(+):CD46 and GTKO porcine aortic EC complementary DNA libraries, respectively. Sequence analysis identified porcine CD9, CD46, CD59, and the EC protein C receptor. We also identified porcine annexin A2 and a glycosyltransferase with homology to the human beta 1,4 N-acetylgalactosaminyl transferase 2 gene.Conclusion. The identified proteins include key EC functions and suggest that non-Gal antibody responses may compromise EC functions and thereby contribute to DXR. Recovery of the porcine beta 1,4 N-acetylgalactosaminyl transferase 2 suggests that an antibody response to a SDa-like carbohydrate may represent a new carbohydrate moiety involved in xenotransplantation. The identification of these porcine gene products may lead to further donor modification to enhance resistance to DXR and further reduce the level of xenograft antigenicity.

Type:Article
Title:Identification of New Carbohydrate and Membrane Protein Antigens in Cardiac Xenotransplantation
DOI:10.1097/TP.0b013e318203c27d
Keywords:Xenotransplantation, Cardiac, Antigen, NON-GAL ANTIGENS, ANTIPHOSPHOLIPID SYNDROME, ANTIBODIES, BABOONS, EXPRESSION, REJECTION, ENDOTHELIUM, COAGULATION, RECEPTOR, MONKEYS
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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