Homocitrullinated keratin, type II cytoskeletal 8 (H-KRT8) (H-KRT8)

Homocitrullinated keratin, type II cytoskeletal 8 (H-KRT8) is a post-translationally modified protein resulting from the carbamylation of lysine residues in cytokeratin 8. This modification is typically triggered by cellular stress, such as nutrient deprivation or inflammation, which increases cyanate levels and promotes the conversion of lysine to homocitrulline (Mydel et al., 2010). In oncology, H-KRT8 acts as a neoantigen because these modified epitopes are selectively presented by tumor cells and are absent in healthy, non-stressed tissues (Brentville et al., 2020). Therapeutic approaches like Scancell's Modi-2 vaccine target these homocitrullinated peptides to stimulate a robust CD4+ T-cell mediated immune response against various cancers, including triple-negative breast cancer and ovarian cancer (Scancell, 2024). Additionally, H-KRT8 is a well-characterized autoantigen in rheumatoid arthritis, where the presence of anti-carbamylated protein (anti-CarP) antibodies is associated with increased joint damage and a more severe disease course (UniProt P05787).

Other names

Carbamylated cytokeratin 8Homocitrullinated CK8Carbamylated KRT8H-CK8

Induction of MHC class II-restricted CD4+ T-cell responses against homocitrullinated neoepitopes presented on the surface of stressed cells (Brentville et al., 2020).