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Induction of antigen-specific tolerance by nanobody-antigen adducts that target class-II major histocompatibility complexes

Item Type:Article
Title:Induction of antigen-specific tolerance by nanobody-antigen adducts that target class-II major histocompatibility complexes
Creators Name:Pishesha, N. and Harmand, T. and Smeding, L.Y. and Ma, W. and Ludwig, L.S. and Janssen, R. and Islam, A. and Xie, Y.J. and Fang, T. and McCaul, N. and Pinney, W. and Sugito, H.R. and Rossotti, M.A. and Gonzalez-Sapienza, G. and Ploegh, H.L.
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:Animals, Mice
Source:Nature Biomedical Engineering
ISSN:2157-846X
Publisher:Nature Publishing Group
Date:14 June 2021
Official Publication:https://doi.org/10.1038/s41551-021-00738-5
PubMed:View item in PubMed

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