Epitopes described in "Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection."

Article Authors:Carolina Boni; Paola Fisicaro; Caterina Valdatta; Barbara Amadei; Paola Di Vincenzo; Tiziana Giuberti; Diletta Laccabue; Alessandro Zerbini; Albertina Cavalli; Gabriele Missale; Antonio Bertoletti; Carlo Ferrari
Article Title:Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection.
Reference Detail
Reference ID:1003526
Abstract:Dysfunctional CD8+ T cells present in chronic virus infections can express programmed death 1 (PD-1) molecules, and the inhibition of the engagement of PD-1 with its ligand (PD-L1) has been reported to enhance the antiviral function of these T cells. We took advantage of the wide fluctuations in levels of viremia which are typical of chronic hepatitis B virus (HBV) infection to comprehensively analyze the impact of prolonged exposure to different virus quantities on virus-specific T-cell dysfunction and on its reversibility through the blocking of the PD-1/PD-L1 pathway. We confirm that chronic HBV infection has a profound effect on the HBV-specific T-cell repertoire. Despite the use of a comprehensive panel of peptides covering all HBV proteins, HBV-specific T cells were rarely observed directly ex vivo in samples from patients with chronic infection, in contrast to those from patients with acute HBV infection. In chronic HBV infection, virus-specific T cells were detected mainly in patients with lower levels of viremia. These HBV-specific CD8+ T cells expressed PD-1, and their function was improved by the blocking of PD-1/PD-L1 engagement. Thus, a broad spectrum of anti-HBV immunity is expressed by patients with chronic HBV infection and this spectrum is proportional to HBV replication levels and can be improved by blocking the PD-1/PD-L1 pathway. This information may be useful for the design of immunotherapeutic strategies to complement and optimize available antiviral therapies.
Affiliations:Laboratorio Immunopatologia Virale, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, via Gramsci 14, 43100 Parma, Italy.
Reference Type:Literature
PubMed ID:17287266
Journal:J Virol
Journal Volume:81
Article Pages:4215-25
Journal ISSN:1098-5514
Article Chemical List:Antigens, CD;Antigens, CD274;Apoptosis Regulatory Proteins;CD274 protein, human;PDCD1 protein, human;Programmed Cell Death 1 Receptor
Article MeSH List:Antigens, CD(analysis; immunology); Antigens, CD274; Apoptosis Regulatory Proteins(analysis; antagonists & inhibitors); CD8-Positive T-Lymphocytes(immunology); Cells, Cultured; Hepatitis B(immunology; virology); Hepatitis B virus(immunology); Hepatitis B, Chronic(immunology; virology); Humans; Immune Tolerance; Leukocytes, Mononuclear; Longitudinal Studies; Programmed Cell Death 1 Receptor; T-Lymphocyte Subsets(immunology); Viremia
Curation Last Updated:2015-07-24 20:07:12