The structure of a LAIR1-containing human antibody reveals a novel mechanism of antigen recognition

ELife
Fu-Lien Hsieh, Matthew K Higgins

Abstract

Antibodies are critical components of the human adaptive immune system, providing versatile scaffolds to display diverse antigen-binding surfaces. Nevertheless, most antibodies have similar architectures, with the variable immunoglobulin domains of the heavy and light chain each providing three hypervariable loops, which are varied to generate diversity. The recent identification of a novel class of antibody in humans from malaria endemic regions of Africa was therefore surprising as one hypervariable loop contains the entire collagen-binding domain of human LAIR1. Here, we present the structure of the Fab fragment of such an antibody. We show that its antigen-binding site has adopted an architecture that positions LAIR1, while itself being occluded. This therefore represents a novel means of antigen recognition, in which the Fab fragment of an antibody acts as an adaptor, linking a human protein insert with antigen-binding potential to the constant antibody regions which mediate immune cell recruitment.

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Citations

Aug 30, 2019·Nature Reviews. Immunology·Jean-Philippe Julien, Hedda Wardemann
Jul 11, 2020·Nature·Thomas E HarrisonMatthew K Higgins
Dec 2, 2020·Proceedings of the National Academy of Sciences of the United States of America·Thomas E HarrisonMatthew K Higgins
Mar 23, 2021·Nature Communications·Emiko MiharaJunichi Takagi

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Methods Mentioned

BETA
glycosylation
glycosyation
NMR
PCR
size-exclusion chromatography

Software Mentioned

Abcheck
AREAIMOL
Coot
Phaser
CCP4
XDS

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