An in vivo selection-derived d-peptide for engineering erythrocyte-binding antigens that promote immune tolerance
<jats:p>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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Proceedings of the National Academy of Sciences
2021
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| Online Access: | https://hdl.handle.net/1721.1/133529 |
| _version_ | 1826215620933320704 |
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| author | 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 Ploegh, Hidde Irvine, Darrell J Pentelute, Bradley L |
| author_facet | 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 Ploegh, Hidde Irvine, Darrell J Pentelute, Bradley L |
| author_sort | Loftis, Alexander R |
| collection | MIT |
| description | <jats:p>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 <jats:sc>d</jats:sc>-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, <jats:italic>K</jats:italic><jats:sub>d</jats:sub>. 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<jats:sup>+</jats:sup> 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.</jats:p> |
| first_indexed | 2024-09-23T16:36:48Z |
| format | Article |
| id | mit-1721.1/133529 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T16:36:48Z |
| publishDate | 2021 |
| publisher | Proceedings of the National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/1335292021-10-28T03:09:03Z An in vivo selection-derived d-peptide for engineering erythrocyte-binding antigens that promote immune tolerance 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 Ploegh, Hidde Irvine, Darrell J Pentelute, Bradley L <jats:p>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 <jats:sc>d</jats:sc>-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, <jats:italic>K</jats:italic><jats:sub>d</jats:sub>. 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<jats:sup>+</jats:sup> 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.</jats:p> 2021-10-27T19:53:22Z 2021-10-27T19:53:22Z 2021-08-24 2021-09-03T16:42:18Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/133529 en 10.1073/pnas.2101596118 Proceedings of the National Academy of Sciences 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. application/pdf Proceedings of the National Academy of Sciences PNAS |
| spellingShingle | 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 Ploegh, Hidde Irvine, Darrell J Pentelute, Bradley L An in vivo selection-derived d-peptide for engineering erythrocyte-binding antigens that promote immune tolerance |
| title | An in vivo selection-derived d-peptide for engineering erythrocyte-binding antigens that promote immune tolerance |
| title_full | An in vivo selection-derived d-peptide for engineering erythrocyte-binding antigens that promote immune tolerance |
| title_fullStr | An in vivo selection-derived d-peptide for engineering erythrocyte-binding antigens that promote immune tolerance |
| title_full_unstemmed | An in vivo selection-derived d-peptide for engineering erythrocyte-binding antigens that promote immune tolerance |
| title_short | An in vivo selection-derived d-peptide for engineering erythrocyte-binding antigens that promote immune tolerance |
| title_sort | in vivo selection derived d peptide for engineering erythrocyte binding antigens that promote immune tolerance |
| url | https://hdl.handle.net/1721.1/133529 |
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