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

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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 Name:	Pishesha, N., Harmand, T., Smeding, L.Y., Ma, W., Ludwig, L.S., Janssen, R., Islam, A., Xie, Y.J., Fang, T., McCaul, N., Pinney, W., Sugito, H.R., Rossotti, M.A., 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:	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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