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Title: | SOLVING THE STRUCTURAL BASIS FOR ALLOANTIBODY RECOGNITION OF ASIAN HLA IN SOLID ORGAN TRANSPLANTATION | Authors: | GU YUE | ORCID iD: | orcid.org/0000-0002-8433-9604 | Keywords: | Antibody; HLA; Transplantation | Issue Date: | 20-Aug-2019 | Citation: | GU YUE (2019-08-20). SOLVING THE STRUCTURAL BASIS FOR ALLOANTIBODY RECOGNITION OF ASIAN HLA IN SOLID ORGAN TRANSPLANTATION. ScholarBank@NUS Repository. | Abstract: | Donor-specific antibodies (DSA), mostly targeting foreign human leukocyte antigens (HLA) are proposed to cause transplant rejections. Our knowledge on alloantibody-HLA interaction relies heavily on in silico modelling. Many studies have reported issues such as false negative results with clinical alloantibody detection assays. In this project, we describe an in-depth biophysical, structural and functional characterization of a human monoclonal alloantibody named 2E3, which binds to HLA-A*11:01. We present the first crystal structure of an alloantibody Fab-HLA complex and highlight its correlation with 2E3 allele specificity. By testing different IgG subclasses of 2E3 at physiological concentrations, we evaluated the clinical assays and proposed reasons behind the false negative results. Our results pave the way for detailed characterization of monoclonal anti-HLA alloantibodies, which could greatly enhance our understanding of anti-HLA alloresponses. Conclusions drawn from clinical assay evaluation can improve our interpretation of the assay results thus lead to better management of transplant recipients. | URI: | https://scholarbank.nus.edu.sg/handle/10635/164182 |
Appears in Collections: | Ph.D Theses (Open) |
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