Tumor-associated antigen-Major Histocompatibility Complex class I complex (TAA-MHC I)

Tumor-associated antigen-Major Histocompatibility Complex (MHC) class I complexes are essential targets for modern cancer immunotherapy, representing the presentation of intracellular protein fragments on the cell surface (Dhatchinamoorthy et al., 2021, Molecular Cancer). These complexes are formed when degraded cytosolic proteins, including those that are mutated (neoantigens) or overexpressed in cancer, are transported into the endoplasmic reticulum and loaded onto MHC class I molecules for display to CD8+ cytotoxic T-lymphocytes (Janeway et al., 2001, Immunobiology). By targeting these complexes, therapeutic agents such as T-cell receptor (TCR) engineered T-cells and TCR-bispecific engagers can recognize and eliminate tumor cells based on their internal proteomic profile, which is inaccessible to traditional monoclonal antibodies (D'Angelo et al., 2024, The Lancet). This approach expands the range of targetable proteins beyond surface-expressed receptors to include transcription factors and metabolic enzymes. However, the efficacy of these therapies is often restricted to specific HLA haplotypes, such as HLA-A*02:01, and significant safety risks exist if the targeted peptide sequence is shared with proteins in vital healthy organs (Nathan et al., 2021, NEJM). Additionally, tumors may develop resistance through the downregulation of MHC expression or components of the antigen processing machinery (Dhatchinamoorthy et al., 2021).

Other names

pMHC class I complexHLA-peptide complexTumor-associated antigen-HLA complexNeoantigen-MHC complexTumor-specific antigen-MHC complex

T-cell receptor (TCR) mediated recognition of peptide-MHC complexes leading to T-cell activation and tumor cell lysis (Nathan et al., 2021; D'Angelo et al., 2024).