1. Host ethnicity and virus genotype shape the hepatitis B virus-specific T-cell repertoire.
- Author
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Tan AT, Loggi E, Boni C, Chia A, Gehring AJ, Sastry KS, Goh V, Fisicaro P, Andreone P, Brander C, Lim SG, Ferrari C, Bihl F, and Bertoletti A
- Subjects
- Asian People, Epitopes, T-Lymphocyte immunology, Flow Cytometry, Genotype, Hepatitis B virus classification, Humans, Interferon-gamma biosynthesis, T-Lymphocyte Subsets immunology, White People, CD8-Positive T-Lymphocytes immunology, Hepatitis B virus genetics, Hepatitis B virus immunology, Hepatitis B, Chronic immunology, Hepatitis B, Chronic virology
- Abstract
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.
- Published
- 2008
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