Taming the TCR: Antigen-Specific Immunotherapeutic Agents for Autoimmune Diseases

Abstract

Current treatments for autoimmune diseases are typically non-specific anti-inflammatory agents that affect not only the autoreactive cells but also the parts of the immune system that are required to maintain health. There is a need for the development of antigen-specific therapeutic agents that can effectively prevent the autoimmune attack while leaving the rest of the immune system functioning as normal. The simplest way to achieve this is using the autoantigen itself as a tolerizing agent; however, there is some risk involved with administering a potentially pathogenic antigen. In this review, we focus instead on the development and use of modified T cell receptor (TCR) ligands, in which the peptide ligand is modified to change the response by the T cell from a disease inducing to a protective response, and still retain the antigen-specificity necessary to target the autoreactive T cells. We review the use of modified TCR ligands as therapeutic agents in animal models of autoimmunity and in human autoimmune disease, and finally consider how they need to be improved in order to use them effectively in patients with autoimmune disease.

Deep sequencing of the T cell receptor β repertoire reveals signature patterns and clonal drift in atherosclerotic plaques and patients

“…Therefore, the composition and structure of the TCR repertoire not only directly affects the function of T cells but also reflects the interaction between genetic and environmental factors. The abnormalities of TCR repertoires are often associated with the development of many immune diseases [ 18 ]. In the peripheral T cells of patients with T2DM, the utilization of the V or J genes (especially TRBV7-8) and the amino acid lengths of the TCR CDR3 regions were significantly altered.…”

Anti-double Stranded DNA Antibodies: Origin, Pathogenicity, and Targeted Therapies

“…These peptides can be synthesized by combining desired amino acid residues or by chemical modification of certain sequences, to ensure higher activity and specificity. To date, therapeutic peptides have proven to be effective against experimental autoimmune diseases, for example, rheumatoid arthritis and multiple sclerosis (133). Moreover, some therapeutic peptides have been demonstrated to prevent anti-dsDNA antibodies from binding and reacting with target antigens and tissues in the studies on SLE.…”

Characterizing how glycerol monolaurate (GML) affects human T cell signaling and function

“…This signaling pathway is integral for all stages of T cell development and the activation of mature T cell effector functions. Pharmacologic modulators of this signaling pathway are under investigation or currently used to treat a variety of diseases including select cancers and autoimmune diseases [14][15][16]. Hence, understanding the mechanism of TCR induced signaling and characterizing how various compounds modulate this pathway can provide significant insight into both physiologic and pathologic T cell responses and explore therapeutic targets to ameliorate many T cell mediated diseases.…”