Neoantigen peptide–HLA class I complex (pHLA-I complex)

The Neoantigen peptide–HLA class I complex is a molecular assembly on the surface of tumor cells consisting of a mutant peptide, derived from non-synonymous somatic mutations, bound to a Human Leukocyte Antigen (HLA) class I molecule. This complex serves as a critical signal for the immune system, specifically allowing CD8+ cytotoxic T lymphocytes to distinguish malignant cells from healthy ones through T-cell receptor (TCR) recognition. Because neoantigens are not present in normal tissues, they are highly specific targets for immunotherapy, minimizing the risk of central tolerance and autoimmune reactions. Therapeutic strategies targeting this complex include personalized vaccines that prime the immune system to recognize these epitopes, TCR-engineered T cells (TCR-T) that directly target the complex, and bispecific molecules that bridge T cells to the tumor. However, challenges such as HLA loss and the high degree of patient-specific polymorphism in HLA alleles complicate the development of universal therapies and require sophisticated prioritization algorithms for effective targeting.

Other names

Neoantigen-MHC class I complexTumor-specific antigen-HLA complexMutant peptide-HLA complexNeoepitope-HLA complexMHC-restricted neoantigenNeoantigen-HLA-I complex

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