An in vivo selection-derived d-peptide for engineering erythrocyte-binding antigens that promote immune tolerance
Name
e2101596118.full.pdf
Description
Published version
Size
1.17 MB
Format
Unknown
Checksum (MD5)
50f5285398a4b7ad2a76b0aed3f4fc52
Author(s)
Loftis, Alexander R
Zhang, Genwei
Backlund, Coralie
Quartararo, Anthony J
Pishesha, Novalia
Hanna, Cameron C
Schissel, Carly K
Garafola, Daniel
Loas, Andrei
Collier, R John
Date Issued
August 2021
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Version
Final published version
Abstract
When displayed on erythrocytes, peptides and proteins can drive antigen-specific immune tolerance. Here, we investigated a straightforward approach based on erythrocyte binding to promote antigen-specific tolerance to both peptides and proteins. We first identified a robust erythrocyte-binding ligand. A pool of one million fully d-chiral peptides was injected into mice, blood cells were isolated, and ligands enriched on these cells were identified using nano-liquid chromatography–tandem mass spectrometry. One round of selection yielded a murine erythrocyte-binding ligand with an 80 nM apparent dissociation constant, Kd. We modified an 83-kDa bacterial protein and a peptide antigen derived from ovalbumin (OVA) with the identified erythrocyte-binding ligand. An administration of the engineered bacterial protein led to decreased protein-specific antibodies in mice. Similarly, mice given the engineered OVA-derived peptide had decreased inflammatory anti-OVA CD8+ T cell responses. These findings suggest that our tolerance-induction strategy is applicable to both peptide and protein antigens and that our in vivo selection strategy can be used for de novo discovery of robust erythrocyte-binding ligands.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Biological Engineering
Ragon Institute of MGH, MIT and Harvard
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Howard Hughes Medical Institute
Massachusetts Institute of Technology. Center for Environmental Health Sciences
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.2101596118
