Regulatory T cell induction via peptide-major histocompatibility complex nanoparticle

Regulatory T cell induction via peptide-major histocompatibility complex (pMHC) nanoparticle refers to a therapeutic strategy that uses nanoparticles coated with disease-relevant pMHC complexes to selectively reprogram antigen-experienced T cells into regulatory T cells (Tregs). This approach aims to suppress autoimmune responses in an antigen-specific manner without broadly impairing normal immune function. The nanoparticles engage cognate T cell receptors (TCRs) on autoantigen-experienced CD4+ or CD8+ T cells, leading to signal amplification and reprogramming of these effector/memory-like autoreactive T cells into regulatory phenotypes, such as IL-10-producing Tr1-like regulatory CD4+ T cells or anergic/regulatory CD8+ cells. The induced regulatory cells can suppress local inflammation and recruit other immune cell types, forming a network that enforces tissue-specific tolerance while sparing systemic immunity. Key parameters influencing efficacy include intermolecular distance between pMHC molecules, stability/safety profile, and the choice between MHC class I vs. II. While most data are preclinical, some related approaches using PLG nanoparticles loaded with peptide antigens have advanced to early-phase clinical trials for autoimmunity indications.

Other names

pMHC nanoparticle therapyTreg induction via pMHC-NPAutoantigen-specific tolerance induction

Reprogramming pathogenic/effector/memory-like autoreactive lymphocytes into regulatory phenotype(s) via sustained multivalent engagement