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

Autor: Gu Y; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; NUS Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore, Singapore, Singapore.; Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Wong YH; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.; NTU Institute of Structural Biology, Nanyang Technological University, Singapore, Singapore., Liew CW; NTU Institute of Structural Biology, Nanyang Technological University, Singapore, Singapore., Chan CEZ; DSO National Laboratories, Singapore, Singapore., Murali TM; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Yap J; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Too CT; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Purushotorman K; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Hamidinia M; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., El Sahili A; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.; NTU Institute of Structural Biology, Nanyang Technological University, Singapore, Singapore., Goh ATH; National University Centre for Organ Transplantation (NUCOT), National University Hospital, Singapore, Singapore., Teo RZC; National University Centre for Organ Transplantation (NUCOT), National University Hospital, Singapore, Singapore., Wood KJ; Transplantation Research Immunology Group, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK., Hanson BJ; DSO National Laboratories, Singapore, Singapore., Gascoigne NRJ; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; NUS Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore, Singapore, Singapore.; Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Lescar J; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore. Julien@ntu.edu.sg.; NTU Institute of Structural Biology, Nanyang Technological University, Singapore, Singapore. Julien@ntu.edu.sg., Vathsala A; National University Centre for Organ Transplantation (NUCOT), National University Hospital, Singapore, Singapore. mdcva@nus.edu.sg.; Division of Nephrology, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. mdcva@nus.edu.sg., MacAry PA; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. micpam@nus.edu.sg.; NUS Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore, Singapore, Singapore. micpam@nus.edu.sg.; Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. micpam@nus.edu.sg.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2019 Feb 21; Vol. 10 (1), pp. 893. Date of Electronic Publication: 2019 Feb 21.
DOI: 10.1038/s41467-019-08790-1
Abstrakt: 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.
Databáze: MEDLINE
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