Major histocompatibility complex class I molecules presenting tumor-derived peptides (pMHC-I)

Major histocompatibility complex (MHC) class I molecules are cell surface glycoproteins responsible for presenting intracellularly derived peptides to CD8+ cytotoxic T cells (Janeway's Immunobiology). In oncology, these molecules present tumor-derived peptides, which can include neoantigens resulting from somatic mutations or tumor-associated antigens that are overexpressed or aberrantly expressed (Nature Reviews Cancer, 2019). This presentation is a fundamental step in the immune system's ability to recognize and eliminate malignant cells. Therapeutic interventions, such as TCR-engineered T cells (TCR-T) and bispecific TCR-based engagers like Tebentafusp, are designed to specifically recognize these peptide-MHC (pMHC) complexes (NEJM, 2021). However, the effectiveness of these therapies can be limited by tumor-mediated HLA downregulation or the risk of off-target toxicity if the targeted peptide is shared with healthy tissues (Science Translational Medicine, 2013).

Other names

Peptide-MHC class I complexpHLA-ITumor antigen-MHC complexNeoantigen-MHC complexpMHCHLA class I/peptide complex

Binding of therapeutic T-cell receptors (TCRs) or TCR-mimic antibodies to the specific peptide-MHC complex, leading to T-cell mediated lysis of the target cell.