Human leukocyte antigen class I molecules presenting DNAJB1-PRKACA fusion neoepitopes (HLA-DNAJB1-PRKACA)

The DNAJB1-PRKACA fusion protein is the pathognomonic driver of fibrolamellar carcinoma (FLC), a rare and often lethal primary liver cancer that typically affects adolescents and young adults. This fusion results from a ~400 kb deletion on chromosome 19, creating a chimeric protein that retains the amino-terminal J-domain of DNAJB1 and the catalytic domain of PRKACA. Because the fusion junction contains a unique amino acid sequence not found in the normal human proteome, it serves as a highly specific neoantigen. HLA class I molecules on the surface of FLC cells present these junctional peptides (neoepitopes) to the immune system, specifically to CD8+ cytotoxic T cells. This HLA-neoepitope complex is a primary target for precision immunotherapies, including T-cell receptor (TCR)-engineered T-cell therapy and therapeutic peptide vaccines, as it offers a way to selectively eliminate malignant cells while sparing healthy tissue. Research has identified specific HLA alleles, such as HLA-A*02:01 and HLA-B*40:01, that can effectively present these junctional sequences to elicit a robust anti-tumor immune response.

Other names

DNAJB1-PRKACA neoantigenFibrolamellar carcinoma fusion neoepitopeMHC-I/DNAJB1-PRKACA complexDNAJB1-PRKACA junctional peptide-HLA complex

Recognition of the tumor-specific junctional peptide presented by HLA class I molecules by engineered T-cell receptors (TCRs) or vaccine-induced endogenous T cells, leading to the selective lysis of fibrolamellar carcinoma cells.