Structural basis for RIFIN-mediated activation of LILRB1 in malaria (Nature: Arase Lab collabrates )
July 14, 2020
The research group of University of Oxford and Osaka University (led by Hisahi Arase, Prof of IFReC/RIMD) determined a structure of a RIFIN bound to LILRB1.
The Plasmodium species that cause malaria are obligate intracellular parasites, and disease symptoms occur as they replicate within human blood. Despite risking immune detection, the parasite delivers proteins that bind host receptors to infected erythrocyte surfaces. In the causative agent of the most deadly human malaria, Plasmodium falciparum, RIFINs form the largest erythrocyte surface protein family (Fig. 1).
Fig.1 Mechanism of immune escape by P. falciparum (Saito et al. Nature 2017)
Some RIFINs can bind inhibitory immune receptors, acting as targets for unusual antibodies containing a LAIR1 ectodomain, or as ligands for LILRB1. RIFINs potentially dampen human immune responses against malaria.
The research group determined a structure of a RIFIN bound to LILRB1 (Fig. 2). They showed that the RIFIN mimics the natural activating ligand of LILRB1, MHC class I, in its LILRB1-binding mode. Therefore, LILRB1-binding RIFINs suppress NK cell function.
Fig. 2 Binding structure of LILRB1-binding RIFIN (L) and LILRB1-binding MHC I (R)
Journal: Nature (online July 11, 2020)
Title: Structural basis for RIFIN-mediated activation of LILRB1 in malaria
Authors: Thomas E. Harrison, Alexander M. Mørcha, James H. Felceb, Akihito Sakoguchi, Adam J. Reide, Hisashi Arase, Michael L. Dustin and Matthew K. Higgins.