Tumor-associated antigen-derived peptide-Major Histocompatibility Complex class I complex (TAA-pMHC-I)

Tumor-associated antigen-derived peptide-Major Histocompatibility Complex class I (TAA-pMHC-I) complexes are the fundamental units of immune recognition for intracellular oncogenic proteins (Neefjes et al., 2011, Nature Reviews Immunology). These complexes consist of a short peptide fragment, typically 8-11 amino acids in length, derived from tumor-associated antigens (TAAs) that are processed and loaded onto MHC class I molecules for surface display (Blum et al., 2013, Annual Review of Immunology). On tumor cells, these complexes serve as the target for CD8+ cytotoxic T lymphocytes (CTLs), which recognize the specific peptide-MHC combination via their T-cell receptors (TCRs). On dendritic cells, TAA-pMHC-I complexes are formed through cross-presentation, a critical process for priming and activating naive T cells against tumor antigens (Joffre et al., 2012, Nature Reviews Immunology). Therapeutic interventions targeting these complexes include TCR-engineered T-cell therapies (TCR-T) and bispecific T-cell engagers like ImmTACs, which bypass the need for natural TCR recognition (Zhao et al., 2021, Journal of Hematology & Oncology). For instance, Tebentafusp is a bispecific protein that targets the gp100 peptide-HLA-A*02:01 complex to treat uveal melanoma (Nathan et al., 2021, New England Journal of Medicine). The clinical utility of these targets is constrained by the requirement for specific HLA haplotypes and the risk of off-target toxicity if the peptide sequence is shared by proteins in healthy tissues.

Other names

pMHC-I complexPeptide-HLA class I complexTumor antigen-MHC complexpMHCHLA-peptide complex

Recognition and binding by T-cell receptors (TCRs) or TCR-mimetic molecules, which triggers the activation of cytotoxic T lymphocytes and leads to the targeted destruction of cells presenting the specific peptide-MHC complex.