Structural basis of malarial parasite RIFIN-mediated immune escape against LAIR1

Malaria infection by Plasmodium falciparum continues to pose a global threat to the human population. P. falciparum expresses variable erythrocyte surface antigens such as RIFINs. Public antibodies with LAIR1 insertion have been identified from malarial patients against a subset of RIFINs. In this study, we solve a LAIR1-binding RIFIN structure: the complex structures of two RIFINs bound to mutated or wild-type LAIR1 in two distinct patterns. Notably, the two RIFINs engage similar binding sites on LAIR1 with different angles, and the RIFIN-binding sites overlap with the collagen-binding site. Surprisingly, RIFINs use completely different binding sites to bind to LAIR1 or LILRB1, indicating the kaleidoscopic change of RIFINs. We then verify that RIFIN could induce LAIR1-mediated cell signaling, and LAIR1-containing antibodies could block the pathway. The findings of this study provide structural insights into the mechanism of the immune escape of P. falciparum and the endless arms race between parasite and host.