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Novalia Pishesha
Boston Children's Hospital
Corresponding Author
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The association of autoimmune diseases with particular allelic variants of Class II MHC (MHCII) products implicates presentation of the offending self-antigen(s) to T cells. Antigen presenting cells are tolerogenic when they encounter antigen under non-inflammatory conditions. Manipulation of antigen presentation would therefore be a possible intervention to induce antigen-specific tolerance. We show that, under non-inflammatory conditions, systemic administration of a single dose of a nanobody that recognizes MHCII (VHH MHCII) conjugated to the relevant self-antigen affords long-lasting protection against induction of experimental autoimmune encephalitis (EAE), type 1 diabetes (T1D), and rheumatoid arthritis (RA). Co-administration of the VHH MHCII-antigen adduct together with dexamethasone, conjugated to VHH MHCII via a cleavable linker, not only halted progression of established EAE in symptomatic mice but even reverted the severity of EAE, establishing this approach as a potential means of treating autoimmune conditions.
Keywords
autoimmunity, autoimmune diseases, Class II MHC, antibodies, antigen
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There is NO Competing Interest.
This is a list of supplementary files associated with this preprint. Click to download.
- ExtendedDataFigures.pdf
Extended Data Figures
- NovaliaPisheshaSupplementaryFigures.pdf
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See the published version of this preprint at Nature Biomedical Engineering.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Article
Novalia Pishesha
Boston Children's Hospital
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Nature Biomedical Engineering.
Version 1
Posted 11 Feb, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Nature Biomedical Engineering.
The association of autoimmune diseases with particular allelic variants of Class II MHC (MHCII) products implicates presentation of the offending self-antigen(s) to T cells. Antigen presenting cells are tolerogenic when they encounter antigen under non-inflammatory conditions. Manipulation of antigen presentation would therefore be a possible intervention to induce antigen-specific tolerance. We show that, under non-inflammatory conditions, systemic administration of a single dose of a nanobody that recognizes MHCII (VHH MHCII) conjugated to the relevant self-antigen affords long-lasting protection against induction of experimental autoimmune encephalitis (EAE), type 1 diabetes (T1D), and rheumatoid arthritis (RA). Co-administration of the VHH MHCII-antigen adduct together with dexamethasone, conjugated to VHH MHCII via a cleavable linker, not only halted progression of established EAE in symptomatic mice but even reverted the severity of EAE, establishing this approach as a potential means of treating autoimmune conditions.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
There is NO Competing Interest.
This is a list of supplementary files associated with this preprint. Click to download.
- ExtendedDataFigures.pdf
Extended Data Figures
- NovaliaPisheshaSupplementaryFigures.pdf
SI Figures
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