Human leukocyte antigen A*24:02-alpha-fetoprotein (158-166) complex (HLA-A*24:02/AFP158)

The Human leukocyte antigen A*24:02-alpha-fetoprotein (158-166) complex is a specific peptide-major histocompatibility complex (pMHC) consisting of the HLA-A*24:02 class I molecule presenting a 9-amino acid epitope (EYSRRHPQL) derived from alpha-fetoprotein (AFP) (Mizukoshi et al., 2006). AFP is an oncofetal protein that is highly overexpressed in hepatocellular carcinoma (HCC) and other germ cell tumors, while remaining largely absent in healthy adult tissues (Butterfield et al., 2001). Because the HLA-A*24:02 allele is highly prevalent in East Asian populations, this complex represents a critical therapeutic target for a large demographic of patients with liver cancer (Gonzalez-Galarza et al., 2020). The complex is primarily targeted by engineered T-cell receptor (TCR) therapies and TCR-mimetic antibodies that recognize the specific spatial configuration of the AFP peptide within the HLA binding groove (He et al., 2022). These therapies aim to redirect the immune system to selectively eliminate AFP-producing malignant cells through T-cell mediated cytotoxicity. Clinical development focuses on ensuring high specificity to avoid cross-reactivity with similar peptides found in normal tissues, which is a primary safety concern for pMHC-targeted agents. Overall, this target provides a pathway for precision immunotherapy in HLA-A*24:02 positive patients with AFP-expressing malignancies.

Other names

HLA-A*24:02 presenting EYSRRHPQLAFP-158/HLA-A*24:02Alpha-fetoprotein-derived epitope EYSRRHPQL in HLA-A*24:02pMHC HLA-A*24:02/AFP158-166

Engineered T-cell receptors or antibodies bind specifically to the peptide-HLA complex on the tumor cell surface, leading to immunological synapse formation and subsequent perforin/granzyme-mediated apoptosis of the target cell.