Radiation-induced mutant peptide–HLA class I complex (RI-neoantigen-HLA-I)

Radiation-induced mutant peptide–HLA class I complexes are specialized molecular targets formed when ionizing radiation induces DNA damage and subsequent mutations in cancer cells (Lhuillier et al., 2021, Cancer Immunology, Immunotherapy). These mutations lead to the synthesis of neoantigens—novel proteins not found in the host's normal proteome—which are then processed and presented on the cell surface by Human Leukocyte Antigen (HLA) class I molecules (Reits et al., 2006, Journal of Experimental Medicine). This presentation allows the immune system, particularly CD8+ cytotoxic T lymphocytes, to distinguish malignant cells from healthy tissue. In clinical oncology, these complexes are leveraged to enhance the efficacy of immunotherapies, as radiotherapy can broaden the range of targetable antigens in tumors with low baseline mutational burdens (Lumniczky et al., 2017, Frontiers in Immunology). Therapeutic strategies targeting these complexes include the development of personalized neoantigen vaccines and T-cell receptor (TCR) engineered therapies designed to recognize specific radiation-induced epitopes.

Other names

Radiation-induced neoantigensRadiation-induced MHC-I associated peptidesRI-mpep-HLA-IRadiation-induced mutant peptide-MHC complexesRadiation-induced immunopeptidome

Recognition of the mutant peptide-HLA complex by specific T-cell receptors (TCRs) on CD8+ T cells, triggering cytotoxic activity and tumor cell lysis.