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Journal of Virology, November 2008, p. 10986-10997, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.01124-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Host Ethnicity and Virus Genotype Shape the Hepatitis B Virus-Specific T-Cell Repertoire ^,

Anthony Tanoto Tan,^1,2 Elisabetta Loggi,³ Carolina Boni,⁴ Adeline Chia,¹ Adam J. Gehring,¹ Konduru S. R. Sastry,¹ Vera Goh,¹ Paola Fisicaro,⁴ Pietro Andreone,³ Christian Brander,^5,6,7 Seng Gee Lim,² Carlo Ferrari,⁴ Florian Bihl,^5,8 and Antonio Bertoletti^1,2,9*

Singapore Institute for Clinical Science, A*STAR, Singapore,¹ Yong Loo Lin School of Medicine, National University of Singapore, Singapore,² Department of Internal Medicine, Cardioangiology and Hepatology, Ospedale S. Orsola-Malpighi, Universita' di Bologna, Bologna, Italy,³ Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy,⁴ Partner AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts,⁵ irsiCaixa Foundation, Hospital Germans Trias i Pujol, Badalona, Spain,⁶ Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain,⁷ Division of Gastroenterology and Hepatology, University Hospital of Geneva, Geneva, Switzerland,⁸ Singapore Immunology Network, ASTAR, Singapore⁹

Received 29 May 2008/ Accepted 5 September 2008

Repertoire composition, quantity, and qualitative functional ability are the parameters that define virus-specific T-cell responses and are linked with their potential to control infection. We took advantage of the segregation of different hepatitis B virus (HBV) genotypes in geographically and genetically distinct host populations to directly analyze the impact that host and virus variables exert on these virus-specific T-cell parameters. T-cell responses against the entire HBV proteome were analyzed in a total of 109 HBV-infected subjects of distinct ethnicities (47 of Chinese origin and 62 of Caucasian origin). We demonstrate that HBV-specific T-cell quantity is determined by the virological and clinical profiles of the patients, which outweigh any influence of race or viral diversity. In contrast, HBV-specific T-cell repertoires are divergent in the two ethnic groups, with T-cell epitopes frequently found in Caucasian patients seldom detected in Chinese patients. In conclusion, we provide a direct biological evaluation of the impact that host and virus variables exert on virus-specific T-cell responses. The discordance between HBV-specific CD8 T-cell repertoires present in Caucasian and Chinese subjects shows the ability of HLA micropolymorphisms to diversify T-cell responses and has implications for the rational development of therapeutic and prophylactic vaccines for worldwide use.

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* Corresponding author. Mailing address: Singapore Institute for Clinical Sciences, A*STAR, Brenner Centre for Molecular Medicine, 30 Medical Drive, Singapore 117609. Phone: (65) 6516 7400. Fax: (65) 6776 6837. E-mail: antonio_bertoletti{at}sics.a-star.edu.sg

Published ahead of print on 17 September 2008.

Supplemental material for this article may be found at http://jvi.asm.org/.

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Journal of Virology, November 2008, p. 10986-10997, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.01124-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.