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

Novalia Pishesha, Thibault Harmand, Liyan Y. Smeding, Weiyi Ma, Leif S. Ludwig, Robine Janssen, Ashraful Islam, Yushu J. Xie, Tao Fang, Nicholas McCaul, William Pinney, Harun R. Sugito, Martin A. Rossotti, Gualberto Gonzalez-Sapienza, Hidde L. Ploegh

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1389-1401
Number of pages13
JournalNature Biomedical Engineering
Volume5
Issue number11
Early online date14 Jun 2021
DOIs
Publication statusPublished - 1 Nov 2021
Externally publishedYes

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