In silico analysis of antibody-carbohydrate interactions and its application to xenoreactive antibodies
Antibody-carbohydrate interactions play central roles in stimulating adverse immune reactions. The most familiar example of such a process is the reaction observed in ABO-incompatible blood transfusion and organ transplantation. The ABO blood groups are defined by the presence of specific carbohydra...
| Main Authors: | , , , , |
|---|---|
| Format: | Journal Article |
| Published: |
2009
|
| Online Access: | http://hdl.handle.net/20.500.11937/20913 |
| _version_ | 1848750442510548992 |
|---|---|
| author | Agostino, Mark Sandrin, M. Thompson, P. Yuriev, E. Ramsland, Paul |
| author_facet | Agostino, Mark Sandrin, M. Thompson, P. Yuriev, E. Ramsland, Paul |
| author_sort | Agostino, Mark |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Antibody-carbohydrate interactions play central roles in stimulating adverse immune reactions. The most familiar example of such a process is the reaction observed in ABO-incompatible blood transfusion and organ transplantation. The ABO blood groups are defined by the presence of specific carbohydrates expressed on the surface of red blood cells. Preformed antibodies in the incompatible recipient (i.e., different blood groups) recognize cells exhibiting host-incompatible ABO system antigens and proceed to initiate lysis of the incompatible cells. Pig-to-human xenotransplantation presents a similar immunological barrier. Antibodies present in humans recognize carbohydrate antigens on the surface of pig organs as foreign and proceed to initiate hyperacute xenograft rejection. The major carbohydrate xenoantigens all bear terminal Gala(1,3)Gal epitopes (or aGal). In this study, we have developed and validated a site mapping technique to investigate protein-ligand recognition and applied it to antibody-carbohydrate systems. This site mapping technique involves the use of molecular docking to generate a series of antibody-carbohydrate complexes, followed by analysis of the hydrogen bonding and van der Waals interactions occurring in each complex. The technique was validated by application to a series of antibody-carbohydrate crystal structures. In each case, the majority of interactions made in the crystal structure complex were able to be reproduced. The technique was then applied to investigate xenoantigen recognition by a panel of monoclonal anti-aGal antibodies. The results indicate that there is a significant overlap of the antibody regions engaging the xenoantigens across the panel. Likewise, similar regions of the xenoantigens interact with the antibodies. © 2009 Elsevier Ltd. All rights reserved. |
| first_indexed | 2025-11-14T07:36:54Z |
| format | Journal Article |
| id | curtin-20.500.11937-20913 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:36:54Z |
| publishDate | 2009 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-209132017-09-13T13:51:04Z In silico analysis of antibody-carbohydrate interactions and its application to xenoreactive antibodies Agostino, Mark Sandrin, M. Thompson, P. Yuriev, E. Ramsland, Paul Antibody-carbohydrate interactions play central roles in stimulating adverse immune reactions. The most familiar example of such a process is the reaction observed in ABO-incompatible blood transfusion and organ transplantation. The ABO blood groups are defined by the presence of specific carbohydrates expressed on the surface of red blood cells. Preformed antibodies in the incompatible recipient (i.e., different blood groups) recognize cells exhibiting host-incompatible ABO system antigens and proceed to initiate lysis of the incompatible cells. Pig-to-human xenotransplantation presents a similar immunological barrier. Antibodies present in humans recognize carbohydrate antigens on the surface of pig organs as foreign and proceed to initiate hyperacute xenograft rejection. The major carbohydrate xenoantigens all bear terminal Gala(1,3)Gal epitopes (or aGal). In this study, we have developed and validated a site mapping technique to investigate protein-ligand recognition and applied it to antibody-carbohydrate systems. This site mapping technique involves the use of molecular docking to generate a series of antibody-carbohydrate complexes, followed by analysis of the hydrogen bonding and van der Waals interactions occurring in each complex. The technique was validated by application to a series of antibody-carbohydrate crystal structures. In each case, the majority of interactions made in the crystal structure complex were able to be reproduced. The technique was then applied to investigate xenoantigen recognition by a panel of monoclonal anti-aGal antibodies. The results indicate that there is a significant overlap of the antibody regions engaging the xenoantigens across the panel. Likewise, similar regions of the xenoantigens interact with the antibodies. © 2009 Elsevier Ltd. All rights reserved. 2009 Journal Article http://hdl.handle.net/20.500.11937/20913 10.1016/j.molimm.2009.09.031 restricted |
| spellingShingle | Agostino, Mark Sandrin, M. Thompson, P. Yuriev, E. Ramsland, Paul In silico analysis of antibody-carbohydrate interactions and its application to xenoreactive antibodies |
| title | In silico analysis of antibody-carbohydrate interactions and its application to xenoreactive antibodies |
| title_full | In silico analysis of antibody-carbohydrate interactions and its application to xenoreactive antibodies |
| title_fullStr | In silico analysis of antibody-carbohydrate interactions and its application to xenoreactive antibodies |
| title_full_unstemmed | In silico analysis of antibody-carbohydrate interactions and its application to xenoreactive antibodies |
| title_short | In silico analysis of antibody-carbohydrate interactions and its application to xenoreactive antibodies |
| title_sort | in silico analysis of antibody-carbohydrate interactions and its application to xenoreactive antibodies |
| url | http://hdl.handle.net/20.500.11937/20913 |