An unusual LAIR1-containing antibody

How do human antibodies co-opt human receptors to recognise variable pathogens?  

Pathogens which live in the blood, such as the malaria parasites, must avoid detection by the immune system. At the same time, they must bind unchanging human molecules to allow them to survive. To achieve this, they are shape shifters, changing the molecules displayed on their surfaces as our bodies learns to recognise them. At the same time, they must retain the critical features required to bind molecules of the human host.

One such group of shape-shifting molecules are the RIFINs from the malaria parasite, Plasmodium falciparum. These are found on the surfaces of malaria infected red blood cells. How can our bodies produce antibodies which recognise these variable RIFINs?

A remarkable trick used by an unusual set of antibodies is to insert a human receptor molecule, LAIR1, into one of its antigen recognition loops. LAIR1 is the human binding partner for a group of RIFINs and LAIR1-containing antibodies bind to and recognise infected blood cells displaying these RIFIN molecules.

Fu-Lien Hsieh decided to solve the structure of a LAIR1 containing antibody to investigate how it works. Antibody molecules normally use six hypervariable loops, which emerge from one surface of the antibody, to recognise pathogens. In the LAIR1 containing antibody, all six of these loops are used to bind and to position LAIR1, suggesting that these antibodies have co-opted LAIR1 and use it to bind to RIFINs. As the function of these RIFINs is to interact with LAIR1, the malaria parasite cannot escape from LAIR1-containing antibodies without losing this receptor binding property.

Only future studies will show how many other antibodies borrow human receptors to allow them to recognise and destroy deadly pathogens. 

Hsieh, F.-L. and Higgins M.K. (2017) The structure of a LAIR1-containing human antibody reveals a novel mechanisms of antigen recognition. eLife 6 e27311