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Differential virus‐specific CD 8 + T‐cell epitope repertoire in hepatitis C virus genotype 1 versus 4
Author(s) -
Luxenburger Hendrik,
Graß Franziska,
Baermann Janina,
Boettler Tobias,
Marget Matthias,
Emmerich Florian,
Panning Marcus,
Thimme Robert,
Nitschke Katja,
NeumannHaefelin Christoph
Publication year - 2018
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.12874
Subject(s) - epitope , genotype , virology , hepatitis c virus , biology , virus , t cell , immunology , antigen , immune system , gene , genetics
Summary Virus‐specific CD 8 + T‐cell responses play an important role in the outcome of hepatitis C virus ( HCV ) infection. To date, most HCV ‐specific CD 8 + T‐cell epitopes have been defined in HCV genotype 1 infection. In contrast, the HCV genotype 4‐specific CD 8 + T‐cell response is poorly defined. Here, we analysed whether known HCV ‐specific CD 8 + T‐cell epitopes are also recognized in HCV genotype 4‐infected patients and set out to identify the first HCV genotype 4‐specific CD 8 + T‐cell epitopes. We studied patients chronically infected with HCV genotype 1 (n = 20) or 4 (n = 21) using 91 well‐described HCV ‐specific epitope peptides. In addition, we analysed 24 genotype 4‐infected patients using 40 epitope candidates predicted using an in silico approach. HCV ‐specific CD 8 + T‐cell responses targeting previously described epitopes were detectable in the majority of genotype 1‐infected patients (11 of 20). In contrast, patients infected with HCV genotype 4 rarely targeted these epitopes (4 of 21; P = .0247). Importantly, we were able to identify eight novel HCV genotype 4‐specific CD 8 + T‐cell epitopes. Only one of these epitopes was shared between genotype 1 and genotype 4. These results indicate that there is little overlap between CD 8 + T‐cell repertoires targeting HCV genotype 1 and 4. Prophylactic vaccination studies based on HCV genotype 1 are currently underway. However, in countries with the highest prevalence of HCV infection, such as Egypt, most patients are infected with HCV genotype 4. Thus, prophylactic vaccination strategies need to be adapted to HCV genotype 4 before their application to regions where HCV genotype 4 is endemic.