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

Authors

  • N. Pishesha
  • T. Harmand
  • L.Y. Smeding
  • W. Ma
  • L.S. Ludwig
  • R. Janssen
  • A. Islam
  • Y.J. Xie
  • T. Fang
  • N. McCaul
  • W. Pinney
  • H.R. Sugito
  • M.A. Rossotti
  • G. Gonzalez-Sapienza
  • H.L. Ploegh

Journal

  • Nature Biomedical Engineering

Citation

  • Nat Biomed Eng 5 (11): 1389-1401

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.


DOI

doi:10.1038/s41551-021-00738-5