Host ethnicity and virus genotype shape the hepatitis B virus-specific T-cell repertoire

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 gene...

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Published in:Journal of virology Vol. 82; no. 22; p. 10986
Main Authors: Tan, Anthony Tanoto, Loggi, Elisabetta, Boni, Carolina, Chia, Adeline, Gehring, Adam J, Sastry, Konduru S R, Goh, Vera, Fisicaro, Paola, Andreone, Pietro, Brander, Christian, Lim, Seng Gee, Ferrari, Carlo, Bihl, Florian, Bertoletti, Antonio
Format: Journal Article
Language:English
Published: United States 15.11.2008
Subjects:
Asian Continental Ancestry Group
CD8-Positive T-Lymphocytes - immunology
Epitopes, T-Lymphocyte - immunology
European Continental Ancestry Group
Flow Cytometry
Genotype
Hepatitis B virus - classification
Hepatitis B virus - genetics
Hepatitis B virus - immunology
Hepatitis B, Chronic - immunology
Hepatitis B, Chronic - virology
Humans
Interferon-gamma - biosynthesis
T-Lymphocyte Subsets - immunology
ISSN:1098-5514, 1098-5514
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Summary: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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ISSN:1098-5514
1098-5514
DOI:10.1128/JVI.01124-08