Human leukocyte antigen A*02:01 in complex with hypoxia-inducible gene 2 peptide (HIG2-9-4) (HLA-A*02:HIG2-9-4)

The HLA-A*02:HIG2-9-4 epitope complex is a peptide-major histocompatibility complex (pMHC) consisting of the HLA-A*02:01 allele and a specific 9-amino acid peptide (YLLPAIVHI) derived from the hypoxia-inducible gene 2 (HIG2) protein, also known as HILPDA (Hypoxia Inducible Lipid Droplet Associated). HIG2 is significantly overexpressed in several cancers, most notably renal cell carcinoma (RCC), where its expression is driven by hypoxia and the VHL-HIF pathway (Togashi et al., 2010, PMID: 20835622). Because HIG2 expression is extremely limited in normal adult tissues, the HLA-A*02:HIG2-9-4 complex serves as a highly tumor-specific antigen. This complex is recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes (CTLs), which then mediate the destruction of the presenting tumor cells. Therapeutic strategies targeting this complex include peptide vaccines, such as the HIG2-9-4 vaccine and the combination vaccine S-288310, which have been evaluated in clinical trials for patients with advanced RCC (Yoshitake et al., 2015, PMID: 25231401). The complex is also a candidate for TCR-engineered T-cell therapies and other modalities designed to exploit its high tumor specificity and prevalence in HLA-A*02:01-positive patients.

Other names

HLA-A*02:01/HIG2-9-4 complexHLA-A*02:01/HILPDA(9-4) complexHIG2-9-4/HLA-A2 complexYLLPAIVHI/HLA-A*02:01Hypoxia-inducible gene 2 epitope

Induction of peptide-specific cytotoxic T lymphocytes (CTLs) that recognize the HIG2-9-4 epitope presented by HLA-A*02:01 on tumor cells, leading to T-cell receptor (TCR) mediated cell lysis.