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Publication : Therapy targeting antigen-specific T cells by a peptide-based tolerizing vaccine against autoimmune arthritis.

First Author  Urbonaviciute V Year  2023
Journal  Proc Natl Acad Sci U S A Volume  120
Issue  25 Pages  e2218668120
PubMed ID  37307481 Mgi Jnum  J:343499
Mgi Id  MGI:7567357 Doi  10.1073/pnas.2218668120
Citation  Urbonaviciute V, et al. (2023) Therapy targeting antigen-specific T cells by a peptide-based tolerizing vaccine against autoimmune arthritis. Proc Natl Acad Sci U S A 120(25):e2218668120
abstractText  A longstanding goal has been to find an antigen-specific preventive therapy, i.e., a vaccine, for autoimmune diseases. It has been difficult to find safe ways to steer the targeting of natural regulatory antigen. Here, we show that the administration of exogenous mouse major histocompatibility complex class II protein bounding a unique galactosylated collagen type II (COL2) peptide (A(q)-galCOL2) directly interacts with the antigen-specific TCR through a positively charged tag. This leads to expanding a VISTA-positive nonconventional regulatory T cells, resulting in a potent dominant suppressive effect and protection against arthritis in mice. The therapeutic effect is dominant and tissue specific as the suppression can be transferred with regulatory T cells, which downregulate various autoimmune arthritis models including antibody-induced arthritis. Thus, the tolerogenic approach described here may be a promising dominant antigen-specific therapy for rheumatoid arthritis, and in principle, for autoimmune diseases in general.
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