Citrullinated antigen-specific regulatory T cell receptor (Cit-specific Treg TCR)

Citrullinated antigen-specific regulatory T cell receptors (TCRs) are specialized immune receptors that recognize post-translationally modified self-antigens, specifically those where arginine residues have been converted to citrulline by peptidylarginine deiminase (PAD) enzymes (nih.gov) [1.1.1, 1.1.3]. In healthy individuals, regulatory T cells (Tregs) expressing these receptors maintain peripheral tolerance by suppressing immune responses against citrullinated proteins (aacrjournals.org) [1.1.1, 1.3.4]. However, in autoimmune conditions like rheumatoid arthritis (RA), there is a breakdown in this tolerance, leading to the development of anti-citrullinated protein antibodies (ACPAs) and the activation of pathogenic effector T cells (nih.gov) [1.1.2, 1.1.5]. Therapeutic strategies targeting these receptors involve the use of engineered cell therapies, such as CAR-Tregs or TCR-Tregs, which are modified to express receptors specific for citrullinated antigens like vimentin or fibrinogen (oup.com, nih.gov) [1.3.1, 1.3.3]. These engineered cells, such as the investigational product SBT-77-7101, are designed to home to inflamed tissues where citrullinated proteins accumulate, such as the synovium in RA (packgene.com, businesswire.com) [1.2.1, 1.2.2]. Upon engagement with their target antigen, these Tregs exert potent immunosuppressive effects through the secretion of anti-inflammatory cytokines (e.g., IL-10, TGF-beta), metabolic disruption of effector cells, and bystander suppression, thereby restoring immune homeostasis without the need for broad systemic immunosuppression (aacrjournals.org, patsnap.com, mdnewsline.com) [1.3.4, 1.4.3, 1.4.4].

Other names

Citrulline-specific T cell receptorAnti-citrullinated protein antigen-specific TCRCitP-specific TCRCit-Treg receptorCitrullinated vimentin-specific CARCitP-specific CAR

Engineered regulatory T cells (Tregs) expressing these receptors recognize citrullinated neo-antigens in inflamed tissues, triggering the secretion of suppressive cytokines (IL-10, TGF-beta) and bystander suppression of effector T and B cells to restore immune tolerance.