8RLV

TCR in complex with HLA-E*01:03 bound to HBV envelope 371-379 L6I peptide

Summary for 8RLV

• Entry DOI: 10.2210/pdb8rlv/pdb
• Descriptor: HLA class I histocompatibility antigen, alpha chain E, Beta-2-microglobulin, Large envelope protein, ... (6 entities in total)
• Functional Keywords: tcr-mhc, tcr, hla-e, hbv, affinity matured, phla, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 10
• Total formula weight: 188193.16

Authors

Pengelly, R.J.,Godinho, L.F. (deposition date: 2024-01-03, release date: 2024-10-16, Last modification date: 2025-02-12)

Primary citation

Murugesan, G.,Paterson, R.L.,Kulkarni, R.,Ilkow, V.,Suckling, R.J.,Connolly, M.M.,Karuppiah, V.,Pengelly, R.,Jadhav, A.,Donoso, J.,Heunis, T.,Bunjobpol, W.,Philips, G.,Ololade, K.,Kay, D.,Sarkar, A.,Barber, C.,Raj, R.,Perot, C.,Grant, T.,Treveil, A.,Walker, A.,Dembek, M.,Gibbs-Howe, D.,Hock, M.,Carreira, R.J.,Atkin, K.E.,Dorrell, L.,Knox, A.,Leonard, S.,Salio, M.,Godinho, L.F.
Viral sequence determines HLA-E-restricted T cell recognition of hepatitis B surface antigen.
Nat Commun, 15:10126-10126, 2024

PubMed 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 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 peptides, we demonstrate that only the most stable Env variant, L6I, elicits functional responses to a09b08-anti-CD3-redirected polyclonal T cells co-cultured with targets expressing endogenous HBsAg. Furthermore, HLA-E-Env L6I-specific CD8 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.

PubMed: 39578466
DOI: 10.1038/s41467-024-54378-9

Experimental method

X-RAY DIFFRACTION (2.609 Å)