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In Gut, two compelling papers1 2 provide novel insights into the complexity of HBV-specific T-cell responses through a detailed analysis of whether T-cell immunity targeting different HBV proteins in HBV-infected patients might exhibit distinct features.
CD8 T cells are a major component of antiviral immunity. Through their ability to recognise and target the cells where viral replication occurs, they can block and even terminate the spread of viral infection in the host. Their highly selective recognition is mediated by the T-cell receptor (TCR) which detects HLA-class I/viral peptide complexes on the cell surface. These protein complexes are made by short viral peptides generated by the processing of viral proteins synthesised within the infected cells (called epitopes) non-covalently associated with HLA-class I molecules. The recognition of viral peptide/HLA complexes by the specific TCR activates the CD8 T cells, which can directly lyse the virus-producing cell or secrete cytokines that inhibit virus replication occurring in the targeted cells.3 Since viruses produce different viral proteins, CD8 T cells are armed with distinct TCRs that recognise epitopes derived from different proteins, and this multispecificity of CD8 T cells should provide the host with a greater chance to effectively control the virus infection.
This is a paradigm in HBV infection, where CD8 T cells have been shown to have a crucial role in the sustained viral control4 and where the ability to mount a multispecific CD8 T-cell response against epitopes derived from different HBV proteins is present in patients with self-limited hepatitis B.5 6 Conversely, patients with chronic HBV are characterised by a defect in the number, specificity and function of HBV-specific CD8 T cells (reviewed in Bertoletti and Ferrari7).
Immunological characterisation in HBV-infected patients to date has supported this neat dichotomy of HBV-specific CD8 T-cell response in different …
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Contributors Both authors contributed to the writing of this commentary.
Funding This work was supported by a Singapore Translational Research (STaR) investigator award (NMRC/STaR/Nov 004/2018) of National Medical Research Council of Singapore to AB and a Barts and The London Charity Large Project grant (723/1795) to PTFK.
Competing interests AB receives research support from Gilead Sciences to test the effect of HBV antigens on immune cell function. He acted as a consultant and served on the advisory boards of Gilead Sciences, Janssen-Cilag, Vir, HUMABS BioMed, SpringBank and Jiangsu Simcere Pharmaceutical. He is also a cofounder of Lion TCR, a biotech company developing T-cell receptors for treatment of virus-related cancers. PTFK has collaborative grant funding from Gilead Sciences, participates in advisory board/provides consultancy to Gilead Sciences and Janssen, and is an investigator for industry-led trials with Gilead Sciences, Janssen, Alere and Assembly Biosciences.
Provenance and peer review Commissioned; internally peer reviewed.
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