Liver, Pancreas, and Biliary TractDirect ex vivo analysis of hepatitis B virus-specific CD8+ T cells associated with the control of infection☆,☆☆,★
Section snippets
Patients and controls
Twenty-three adult subjects (18 male and 5 female; age range, 24–54 years) with self-limited acute HBV infection were studied. Diagnosis of acute hepatitis was based on increased serum alanine aminotransferase (ALT) activity (at least 10 times the upper limit of normal) and detection of hepatitis B surface (HBsAg) antigen and immunoglobulin (Ig) M anti–hepatitis B core antigen (anti-HBc) antibodies in the serum along with the recent onset of jaundice and associated symptoms. All patients were
Synthesis and characterization of HLA-A2/HBV tetramers
Tetramers of HLA-A2 complexed with peptides from core (amino acids 18–27), polymerase (amino acids 575–583), and envelope (amino acids 335–343) proteins were generated as described previously8 (hereafter indicated as T c18–27, T p575–583, and T e335–343, respectively) to study the HBV-specific CTL response to these dominant epitopes4, 5, 6 during acute HBV infection. The specificity of tetramers was determined using CTL clones2 and CTL lines generated by stimulation of PBMCs from
Discussion
The direct analysis of 14 HLA-A2–positive patients with acute HBV infection using the tetramer technology described in this study provides a quantitative characterization of the kinetics and hierarchy of the HBV-specific CD8 response during a self-limited infection with a noncytopathic virus. The same technology has been applied to the study of other acute viral infections, revealing the potential extent of virus-specific T-cell expansion. Fifty to 70% of CD8+ T cells are virus specific in the
Acknowledgements
The authors thank Ludovica Bruno for comments on the manuscript and help with fluorescence-activated cell sorting; and Peter Beverley, Persephone Borrow, and Jethro Herberg for critical reading of the manuscript.
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2024, Journal of HepatologyEASL International Recognition Award Recipient 2023: Prof. Antonio Bertoletti
2023, Journal of Hepatology
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Address requests for reprints to: Antonio Bertoletti, M.D., Institute of Hepatology, University College London, 69-75 Chenies Mews, London, WC1E 6HX England. e-mail: [email protected]; fax: (44) 171-380-0405.
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Supported by a Collaborative Research Grant from the Edward Jenner Institute for Vaccine Research (to M.K.M.); by the Fondo de Investigaciones Sanitarias (B.E.F.I. 98/9155) from the Ministerio de Sanidad y Consumo of Spain (J.R.L.); and partially supported by a University College London Clinical Research and Development Committee grant.
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M. K. Maini and C. Boni contributed equally to this work.