A highly selective TCR-mimic antibody reveals unexpected mechanisms of HBV peptide-MHC recognition and previously unknown target biology.

ABSTRACT: Curative therapies for chronic hepatitis B virus infection (CHB) are needed, and T-cell redirection is a promising approach, with peptide-MHC complexes (pMHC) being attractive targets. HBV core_18-27 peptide (C18, 10-mer) presented by HLA-A*02:01 (C18-MHC) has two major variants (C18-V or C18-I, differing in the C-terminal residue), both of which are known to be targeted by CD8⁺ T cells in HBV-infected individuals. Through an extensive screening campaign, we identified a highly selective anti-C18-MHC antibody clone MUR35. A MUR35-based T-cell engager (TCE) potently killed HBV-infected hepatocytes but had no activity on uninfected hepatocytes, on other HBV-negative cell types or on host peptides with sequence similarity to C18. Crystal structures of MUR35 bound to both

SUBMITTER: Khan S 

PROVIDER: S-EPMC12461897 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature