T-cell receptor (TCR) recognizing tsRNA-derived peptide–MHC complexes (TCR-tsPEP-MHC)

The T-cell receptor (TCR) recognizing tsRNA-derived peptide–MHC complexes is a specialized immune receptor that identifies a novel class of antigens originating from tRNA-derived small RNAs (tsRNAs). Historically considered non-coding, recent research has demonstrated that tsRNAs can undergo non-canonical, non-AUG-initiated translation to produce small peptides known as tsPEPs. These peptides are processed and presented by MHC class I molecules on the cell surface, where they serve as targets for specific CD8+ T cells. This pathway is particularly significant in oncology, as tsRNAs are frequently dysregulated in various cancers, potentially generating a unique repertoire of tumor-specific neoantigens. Therapeutic strategies targeting these TCR-peptide-MHC interactions include the development of TCR-engineered T-cell (TCR-T) therapies and epitope-based cancer vaccines designed to stimulate a robust anti-tumor immune response. Understanding this mechanism expands the known antigenic landscape and offers new opportunities for precision immunotherapy.

Other names

T-cell receptorTCRtsPEP-specific T-cell receptortRNA-derived peptide-specific TCR

Recognition of specific peptide-MHC complexes, where the peptide is derived from tRNA-derived small RNAs (tsRNAs), on the surface of target cells (e.g., tumor cells), leading to T-cell activation, proliferation, and targeted killing of the cell.