Say No to Transplant Rejection

by | Mar 20, 2020 | Biology, School of Biological Sciences

Hands holding to a heart organ

During organ transplantation, the donor organ is almost always recognised as foreign by the recipient’s immune system. When organ rejection is cell-mediated, it can be treated with steroids. Alloantibody-mediated organ rejection, however, often leads to transplantation failure.

To better understand alloantibody-mediated rejection, which is caused by alloantibodies produced by the transplant recipient binding to human leukocyte antigen (HLA) on the transplanted organ, researchers from NTU and the National University of Singapore resolved the crystal structure of the alloantibody-HLA molecular interaction at 2.4 angstrom (0.24 nanometers) resolution.

From the crystal structure, the team, led by Assoc Prof Julien Lescar of NTU’s School of Biological Sciences, identified amino acids in HLA critical for alloantibody binding. They discovered that the HLA binding site for the alloantibody was some distance away from sites involved in interaction with other immune cells and peptides, indicating that the inflammatory response stimulated by the antibody was independent of HLA’s interaction with other cells and molecules.

This discovery opens the door to designing inhibitors that obstruct antibody-HLA binding, which may help suppress antibody-mediated immune responses and prevent organ rejection, the researchers say.

The research “Defining the structural basis for human alloantibody binding to human leukocyte antigen allele HLA-A*11:01” was published in Nature Communications (2019), DOI: 10.1038/s41467-019-08790-1, and featured in ScienceDaily (2019), bit.ly/SDtransplantres, and Asian Scientist Magazine (2019), bit.ly/AStransplantres.

The article appeared first in NTU’s research & innovation magazine Pushing Frontiers (issue #16, February 2020).