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

Nature Communications
Yue GuPaul A MacAry

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.

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Citations

Nov 23, 2019·International Journal of Immunogenetics·Matthew D Blunt, Salim I Khakoo
Apr 29, 2020·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Cynthia S M KramerSebastiaan Heidt
Jan 12, 2021·International Journal of Immunogenetics·William LemieuxRuth Sapir-Pichhadze
Dec 4, 2019·Current Opinion in Organ Transplantation·Chris Wiebe, Peter W Nickerson
Jun 15, 2021·Frontiers in Pharmacology·Yi-Wu ShiWei-Ping Liao

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Methods Mentioned

BETA
quartz crystal microbalance
enzyme-linked immunosorbent assay
ELISA
flow cytometry
X-ray
biosensor
Protein
size exclusion chromatography
electrophoresis
chips

Software Mentioned

PHENIX
SeqMan
MR
PHASER
BUSTER
FlowJo VX
DNAstar
COOT

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