Autoantigen–MHC complexes recognized by umbilical cord blood regulatory T-cell T-cell receptors (pMHC-TCR (UCB Treg))

Autoantigen–MHC complexes recognized by umbilical cord blood (UCB) regulatory T-cell (Treg) T-cell receptors (TCRs) are critical molecular targets for the induction of antigen-specific immune tolerance in autoimmune diseases. UCB-derived Tregs possess a unique, highly diverse TCR repertoire that is naturally enriched for sequences recognizing self-peptides, such as those from insulin, GAD65, and chromogranin A, presented by MHC Class II molecules like HLA-DR4 and HLA-DQ8. The engagement of these peptide-MHC (pMHC) complexes by Treg TCRs activates suppressive mechanisms, including the production of anti-inflammatory cytokines (e.g., IL-10, TGF-β) and the downregulation of co-stimulatory molecules on antigen-presenting cells. This interaction is being exploited in therapeutic strategies such as the adoptive transfer of ex vivo expanded UCB-Tregs and the development of TCR-engineered Tregs designed to home to inflamed tissues and suppress pathogenic effector T cells. Additionally, pMHC-coated nanoparticles (Navacims) are being investigated to selectively expand these autoreactive Treg populations in vivo, offering a potential for precise, durable immune regulation while avoiding the risks of systemic immunosuppression.

Other names

Self-peptide-MHC complexespMHCII complexesAutoantigen-HLA complexesPeptide-MHC complexesAutoreactive Treg TCR ligands

TCR-mediated immune suppression, induction of regulatory T cell expansion, modulation of antigen-presenting cell function, bystander suppression