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 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.
Tan
Anthony Tanoto
AT
Singapore Institute for Clinical Sciences, A*STAR, Brenner Centre for Molecular Medicine, 30 Medical Drive, Singapore.
Loggi
Elisabetta
E
Boni
Carolina
C
Chia
Adeline
A
Gehring
Adam J
AJ
Sastry
Konduru S R
KS
Goh
Vera
V
Fisicaro
Paola
P
Andreone
Pietro
P
Brander
Christian
C
Lim
Seng Gee
SG
Ferrari
Carlo
C
Bihl
Florian
F
Bertoletti
Antonio
A
D044466:Asian People; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005434:Flow Cytometry; D005838:Genotype; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000821:virology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology; D044465:White People
D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma
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