Induction of antigen-specific tolerance by nanobody-antigen adducts that target class-II major histocompatibility complexes.
Nat Biomed Eng
; 5(11): 1389-1401, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-34127819
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Encefalomielite Autoimune Experimental
/
Tolerância Imunológica
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article