Defining the structural basis for human alloantibody binding to human leukocyte antigen allele HLA-A*11:01
Our understanding of the conformational and electrostatic determinants that underlie targeting of human leukocyte antigens (HLA) by anti-HLA alloantibodies is principally based upon in silico modelling. Here we provide a biochemical/biophysical and functional characterization of a human monoclonal a...
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Main Authors: | , , , , , , , , , , , , , , , , , |
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Other Authors: | |
Format: | Article |
Language: | English |
Published: |
2019
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Subjects: | |
Online Access: | https://hdl.handle.net/10356/105503 http://hdl.handle.net/10220/47817 |
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Institution: | Nanyang Technological University |
Language: | English |
Summary: | Our understanding of the conformational and electrostatic determinants that underlie targeting of human leukocyte antigens (HLA) by anti-HLA alloantibodies is principally based upon in silico modelling. Here we provide a biochemical/biophysical and functional characterization of a human monoclonal alloantibody specific for a common HLA type, HLA-A*11:01. We present a 2.4 Å resolution map of the binding interface of this antibody on HLA-A*11:01 and compare the structural determinants with those utilized by T-cell receptor (TCR), killer-cell immunoglobulin-like receptor (KIR) and CD8 on the same molecule. These data provide a mechanistic insight into the paratope−epitope relationship between an alloantibody and its target HLA molecule in a biological context where other immune receptors are concomitantly engaged. This has important implications for our interpretation of serologic binding patterns of anti-HLA antibodies in sensitized individuals and thus, for the biology of human alloresponses. |
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