Carcinoembryonic antigen-related cell adhesion molecule 5-epitope-specific T-cell receptor on CD8+ regulatory T-cells (CEACAM5-specific CD8+ Treg TCR)

CEACAM5-epitope-specific T-cell receptors (TCRs) are specialized immune receptors expressed on a distinct subset of CD8+ regulatory T cells (Tregs), primarily located in the intestinal mucosa (Roda et al., 2022). These TCRs are responsible for recognizing specific peptide epitopes of Carcinoembryonic Antigen-related Cell Adhesion Molecule 5 (CEACAM5), a glycoprotein traditionally known as a tumor marker but also expressed on normal intestinal epithelial cells (Dunkin et al., 2022). The interaction typically involves the non-classical MHC molecule CD1d, which presents CEACAM5 fragments to the TCR, triggering a suppressive signaling cascade that inhibits the activity of pro-inflammatory CD4+ T cells (Roda et al., 2022). This mechanism is vital for maintaining mucosal tolerance and preventing aberrant immune responses against commensal flora or self-antigens in the gut. In patients with inflammatory bowel diseases (IBD), such as Crohn's disease, the activity of these CEACAM5-specific CD8+ Tregs is significantly diminished, contributing to chronic intestinal inflammation (Dunkin et al., 2022). Conversely, in various adenocarcinomas where CEACAM5 is overexpressed, these regulatory cells may inadvertently protect the tumor from the host's immune system (Onclive, 2022). Therapeutic research is currently exploring CEACAM5-derived peptides as agonists to reactivate these TCRs for the treatment of IBD (Gastroenterology, 2022). Additionally, understanding these TCRs provides insights into how tumors evade the immune system, potentially leading to new strategies in cancer immunotherapy. The targeting of these receptors represents a novel approach to modulating the immune system by leveraging endogenous regulatory pathways. Overall, these TCRs serve as a critical link between epithelial cell signaling and the regulation of adaptive immunity in the gastrointestinal tract.

Other names

CEA-specific CD8+ Treg TCRgp180-reactive T-cell receptorCD1d-restricted CEACAM5-specific TCRCarcinoembryonic antigen-specific suppressor T-cell receptor

Activation of CD8+ regulatory T cells through TCR-mediated recognition of CEACAM5 epitopes, leading to the suppression of CD4+ effector T cell proliferation and cytokine production.