Alpha-fetoprotein peptide–HLA class I major histocompatibility complex (AFP peptide–MHC) complex (AFP peptide–MHC complex)

The alpha-fetoprotein peptide–HLA class I MHC complex is formed when peptides derived from intracellularly-expressed alpha-fetoprotein (an oncofetal glycoprotein highly upregulated in hepatocellular carcinoma and some other solid tumors) are processed and presented by class I major histocompatibility complex (usually HLA-A*02:01) molecules on the cell surface. This complex serves as a highly specific tumor-associated antigen that can be recognized by the immune system, but due to immune tolerance and evasion, natural antitumor responses are often ineffective. Recent immunotherapy strategies have engineered T lymphocytes (such as CAR-T or TCR-T cells) or developed TCR-mimic antibodies to recognize and bind these peptide–MHC complexes, selectively killing AFP-expressing cancer cells while sparing normal tissues. Clinical application requires careful patient selection (AFP positivity and HLA typing) and monitoring for immune-mediated adverse events due to the risk of cross-reactivity. AFP–MHC complexes play critical roles in tumor immunology as both biomarkers and therapeutic targets for innovative, highly specific cancer immunotherapies[1][2][3][4][6][7][8][9].

Other names

AFP–MHC complexAlpha-fetoprotein–HLA complexAFP-derived peptide–MHC complexAFP_158-166 peptide–HLA-A*02:01 complexAFP/HLA-A*02:01 complex

Recognition and binding of AFP peptide–MHC complex on malignant hepatocytes/solid tumor cells by engineered T cells (CAR-T cells or TCR-engineered cells), leading to redirected cytotoxicity and cancer cell lysis. In the case of TCR-mimic (TCRm) antibodies, direct binding to the peptide–MHC complex induces tumor cell death via immune effector mechanisms (e.g., T cell recruitment or direct T cell activation).