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Defining the structural basis for human alloantibody binding to human leukocyte antigen allele HLA-A*11:01

Author

Listed:
  • Yue Gu

    (National University of Singapore
    National University of Singapore
    National University of Singapore)

  • Yee Hwa Wong

    (Nanyang Technological University
    Nanyang Technological University)

  • Chong Wai Liew

    (Nanyang Technological University)

  • Conrad E. Z. Chan

    (DSO National Laboratories)

  • Tanusya M. Murali

    (National University of Singapore
    National University of Singapore)

  • Jiawei Yap

    (National University of Singapore
    National University of Singapore)

  • Chien Tei Too

    (National University of Singapore
    National University of Singapore)

  • Kiren Purushotorman

    (National University of Singapore
    National University of Singapore)

  • Maryam Hamidinia

    (National University of Singapore
    National University of Singapore)

  • Abbas El Sahili

    (Nanyang Technological University
    Nanyang Technological University)

  • Angeline T. H. Goh

    (National University Hospital)

  • Rachel Z. C. Teo

    (National University Hospital)

  • Kathryn J. Wood

    (University of Oxford)

  • Brendon J. Hanson

    (DSO National Laboratories)

  • Nicholas R. J. Gascoigne

    (National University of Singapore
    National University of Singapore
    National University of Singapore)

  • Julien Lescar

    (Nanyang Technological University
    Nanyang Technological University)

  • Anantharaman Vathsala

    (National University Hospital
    National University of Singapore)

  • Paul A. MacAry

    (National University of Singapore
    National University of Singapore
    National University of Singapore)

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.

Suggested Citation

  • Yue Gu & Yee Hwa Wong & Chong Wai Liew & Conrad E. Z. Chan & Tanusya M. Murali & Jiawei Yap & Chien Tei Too & Kiren Purushotorman & Maryam Hamidinia & Abbas El Sahili & Angeline T. H. Goh & Rachel Z. , 2019. "Defining the structural basis for human alloantibody binding to human leukocyte antigen allele HLA-A*11:01," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08790-1
    DOI: 10.1038/s41467-019-08790-1
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