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Title: Defining the structural basis for human alloantibody binding to human leukocyte antigen allele HLA-A*11:01
Authors: Gu, Yue
Wong, Yee Hwa
Liew, Chong Wai
Chan, Conrad E. Z.
Murali, Tanusya M.
Yap, Jiawei
Too, Chien Tei
Purushotorman, Kiren
Hamidinia, Maryam
El Sahili, Abbas
Goh, Angeline T. H.
Teo, Rachel Z. C.
Wood, Kathryn J.
Hanson, Brendon J.
Gascoigne, Nicholas R. J.
Lescar, Julien
Vathsala, Anantharaman
MacAry, Paul A.
Keywords: MHC Class I
DRNTU::Science::Biological sciences
Issue Date: 2019
Source: Gu, Y., Wong, Y. H., Liew, C. W., Chan, C. E. Z., Murali, T. M., Yap, J., . . . MacAry, P. A. (2019). Defining the structural basis for human alloantibody binding to human leukocyte antigen allele HLA-A*11:01. Nature Communications, 10(1), 893-. doi:10.1038/s41467-019-08790-1
Series/Report no.: Nature Communications
Abstract: 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.
DOI: 10.1038/s41467-019-08790-1
Schools: School of Biological Sciences 
Research Centres: NTU Institute of Structural Biology 
Rights: © 2019 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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