Human endogenous retrovirus K-derived peptide presented on human leukocyte antigen (HERV-K peptide-HLA complex)

Human endogenous retrovirus K (HERV-K) represents a family of ancient viral sequences integrated into the human genome, which are generally silenced in healthy tissues but reactivated in various malignancies such as breast cancer, melanoma, and prostate cancer (PMID: 30104345). Peptides derived from HERV-K proteins, such as the envelope (Env) protein, are processed and presented on the cell surface by human leukocyte antigen (HLA) molecules, particularly HLA-A*02:01 (PMID: 26034289). This HERV-K peptide-HLA complex functions as a tumor-specific antigen that can be recognized by the immune system. Therapeutic strategies targeting this complex include T-cell receptor (TCR)-engineered T cells and TCR-like antibodies, which aim to induce a potent cytotoxic response against tumor cells while sparing normal tissue (PMID: 29439110). Because HERV-K expression is highly restricted to malignant cells, it offers a unique opportunity for high-precision immunotherapy. Ongoing research is focused on validating the safety of these targets and expanding the range of targetable HERV-K peptides across different HLA types (PMID: 34571445).

Other names

HERV-K-MHC complexHERV-K-derived antigenHERV-K Env peptide-HLA-A*02:01Human endogenous retrovirus K antigenHERV-K-derived peptide-MHC

Recognition of the specific HERV-K peptide-HLA complex by engineered T-cell receptors (TCRs) or TCR-like antibodies, which triggers T-cell activation, secretion of cytotoxic granules such as perforin and granzymes, and subsequent lysis of the tumor cell (PMID: 26034289).