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| Item Type: | Article |
|---|---|
| Title: | Induction of antigen-specific tolerance by nanobody-antigen adducts that target class-II major histocompatibility complexes |
| Creators: |
Pishesha, N.  ORCID: https://orcid.org/0000-0002-8124-1265, Harmand, T., Smeding, L.Y. ORCID: https://orcid.org/0000-0002-3850-1746, Ma, W., Ludwig, L.S. ORCID: https://orcid.org/0000-0002-2916-2164, Janssen, R., Islam, A., Xie, Y.J., Fang, T., McCaul, N. ORCID: https://orcid.org/0000-0002-7888-7815, Pinney, W., Sugito, H.R., Rossotti, M.A., Gonzalez-Sapienza, G. and Ploegh, H.L. ORCID: https://orcid.org/0000-0002-1090-6071
|
| Abstract: | The association of autoimmune diseases with particular allellic products of the class-II major histocompatibility complex (MHCII) region implicates the presentation of the offending self-antigens to T cells. Because antigen-presenting cells are tolerogenic when they encounter an antigen under non-inflammatory conditions, the manipulation of antigen presentation may induce antigen-specific tolerance. Here, we show that, in mouse models of experimental autoimmune encephalomyelitis, type 1 diabetes and rheumatoid arthritis, the systemic administration of a single dose of nanobodies that recognize MHCII molecules and conjugated to the relevant self-antigen under non-inflammatory conditions confers long-lasting protection against these diseases. Moreover, co-administration of a nanobody-antigen adduct and the glucocorticoid dexamethasone, conjugated to the nanobody via a cleavable linker, halted the progression of established experimental autoimmune encephalomyelitis in symptomatic mice and alleviated their symptoms. This approach may represent a means of treating autoimmune conditions. |
| Keywords: | Autoantigens, Experimental Autoimmune Encephalomyelitis, Histocompatibility, Immune Tolerance, Major Histocompatibility Complex, Animals, Mice |
| Source: | Nature Biomedical Engineering |
| ISSN: | 2157-846X |
| Publisher: | Nature Publishing Group |
| Volume: | 5 |
| Number: | 11 |
| Page Range: | 1389-1401 |
| Date: | November 2021 |
| Official Publication: | https://doi.org/10.1038/s41551-021-00738-5 |
| PubMed: | View item in PubMed |
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