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The structure of a LAIR1-containing human antibody reveals a novel mechanism of antigen recognition
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 hype...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5459573/ https://www.ncbi.nlm.nih.gov/pubmed/28527239 http://dx.doi.org/10.7554/eLife.27311 |
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author | Hsieh, Fu-Lien Higgins, Matthew K |
author_facet | Hsieh, Fu-Lien Higgins, Matthew K |
author_sort | Hsieh, Fu-Lien |
collection | PubMed |
description | 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. DOI: http://dx.doi.org/10.7554/eLife.27311.001 |
format | Online Article Text |
id | pubmed-5459573 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-54595732017-06-07 The structure of a LAIR1-containing human antibody reveals a novel mechanism of antigen recognition Hsieh, Fu-Lien Higgins, Matthew K eLife Immunology 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. DOI: http://dx.doi.org/10.7554/eLife.27311.001 eLife Sciences Publications, Ltd 2017-05-20 /pmc/articles/PMC5459573/ /pubmed/28527239 http://dx.doi.org/10.7554/eLife.27311 Text en © 2017, Hsieh et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Immunology Hsieh, Fu-Lien Higgins, Matthew K The structure of a LAIR1-containing human antibody reveals a novel mechanism of antigen recognition |
title | The structure of a LAIR1-containing human antibody reveals a novel mechanism of antigen recognition |
title_full | The structure of a LAIR1-containing human antibody reveals a novel mechanism of antigen recognition |
title_fullStr | The structure of a LAIR1-containing human antibody reveals a novel mechanism of antigen recognition |
title_full_unstemmed | The structure of a LAIR1-containing human antibody reveals a novel mechanism of antigen recognition |
title_short | The structure of a LAIR1-containing human antibody reveals a novel mechanism of antigen recognition |
title_sort | structure of a lair1-containing human antibody reveals a novel mechanism of antigen recognition |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5459573/ https://www.ncbi.nlm.nih.gov/pubmed/28527239 http://dx.doi.org/10.7554/eLife.27311 |
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