Induction of Antigen-specific Tolerance by Nanobody-antigen Adducts That Target Class-II Major Histocompatibility Complexes

Overview

Journal Nat Biomed Eng

Publisher Springer Nature

Specialty Biomedical Engineering

Date 2021 Jun 15

PMID 34127819

Citations 17

Authors

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 3rd

Harun R Sugito

Martin A Rossotti

Gualberto Gonzalez-Sapienza

Hidde L Ploegh

Affiliations

Soon will be listed here.

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.

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