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

Version of Record: June 5, 2017
Accepted Manuscript: May 20, 2017

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1. Part of Collection
Malaria: A Collection of Articles

Edited by Olivier Silvie et al.

Abstract
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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 an 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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Fu-Lien Hsieh

Department of Biochemistry, University of Oxford, Oxford, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Matthew K Higgins

Department of Biochemistry, University of Oxford, Oxford, United Kingdom

For correspondence
matthew.higgins@bioch.ox.ac.uk

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-2870-1955

Funding

Wellcome (101020/Z/13/Z)

Fu-Lien Hsieh
Matthew K Higgins

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.