Viral sequence determines HLA-E-restricted T cell recognition of hepatitis B surface antigen.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39578466.
- Also identified by DOI 10.1038/s41467-024-54378-9 and PMC identifier 11584656.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The non-polymorphic HLA-E molecule offers opportunities for new universal immunotherapeutic approaches to chronic infectious diseases. Chronic Hepatitis B virus (HBV) infection is driven in part by T cell dysfunction due to elevated levels of the HBV envelope (Env) protein hepatitis B surface antigen (HBsAg). Here we report the characterization of three genotypic variants of an HLA-E-binding HBsAg peptide, Env<sub>371-379,</sub> identified through bioinformatic predictions and verified by biochemical and cellular assays. Using a soluble affinity-enhanced T cell receptor (TCR) (a09b08)-anti-CD3 bispecific molecule to probe HLA-E presentation of the Env<sub>371-379</sub> peptides, we demonstrate that only the most stable Env<sub>371-379</sub> variant, L6I, elicits functional responses to a09b08-anti-CD3-redirected polyclonal T cells co-cultured with targets expressing endogenous HBsAg. Furthermore, HLA-E-Env<sub>371-379</sub> L6I-specific CD8<sup>+</sup> T cells are detectable in HBV-naïve donors and people with chronic HBV after in vitro priming. In conclusion, we provide evidence for HLA-E-mediated HBV Env peptide presentation, and highlight the effect of viral mutations on the stability and targetability of pHLA-E molecules.
Medical subject headings
- Hepatitis B Surface Antigens
- Hepatitis B virus
- CD8-Positive T-Lymphocytes
- Histocompatibility Antigens Class I
- HLA-E Antigens