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

Nature biomedical engineering 2021 Nov

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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. © 2021. The Author(s), under exclusive licence to Springer Nature Limited.

Citation

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. Induction of antigen-specific tolerance by nanobody-antigen adducts that target class-II major histocompatibility complexes. Nature biomedical engineering. 2021 Nov;5(11):1389-1401