Alpha-fetoprotein-derived peptide epitopes presented on HLA class I (AFP-HLA complex)

Alpha-fetoprotein (AFP) is a 70 kDa glycoprotein primarily expressed during fetal development by the yolk sac and liver, which typically declines to trace levels shortly after birth (Source: UniProt P02771). In adults, its re-expression is a hallmark of hepatocellular carcinoma (HCC) and certain germ cell tumors, making it a classic tumor-associated antigen. Intracellular AFP is processed by the proteasome into short peptide fragments, such as the immunodominant AFP158-166 epitope, which are then transported to the cell surface and presented by Human Leukocyte Antigen (HLA) Class I molecules, most commonly HLA-A*02:01 (Source: PubMed PMID: 10438924). This peptide-HLA complex serves as a specific target for immunotherapy, allowing engineered T-cell receptors (TCRs) or TCR-like antibodies to distinguish malignant cells from healthy adult tissue. Therapeutic strategies targeting this complex include TCR-engineered T-cell therapies (TCR-T) and bispecific molecules designed to trigger a potent cytotoxic immune response against AFP-positive tumors (Source: Adaptimmune). By targeting the presented peptide rather than the secreted protein, these therapies can effectively engage the cellular immune system to eliminate tumor cells directly.

Other names

AFP-MHC class I complexAFP-peptide/HLA-A*02:01AFP-pMHCAFP158-166/HLA-A*02:01Alpha-fetoprotein-MHC complex

Engineered T-cell receptors (TCRs) or TCR-like antibodies specifically recognize and bind to the AFP peptide-HLA complex on the tumor cell surface, leading to T-cell activation and subsequent granzyme/perforin-mediated lysis of the target cell (Source: Adaptimmune, NCT03132792).