Journal article
HLA-B∗27 subtype specificity determines targeting and viral evolution of a hepatitis C virus-specific CD8+ T cell epitope
Journal of Hepatology, Vol.60(1), pp.22-29
2013
Abstract
Background & Aims
HLA-B∗27 is associated with spontaneous HCV genotype 1 clearance. HLA-B∗27-restricted CD8+ T cells target three NS5B epitopes. Two of these epitopes are dominantly targeted in the majority of HLA-B∗27+ patients. In chronic infection, viral escape occurs consistently in these two epitopes. The third epitope (NS5B2820) was dominantly targeted in an acutely infected patient. This was in contrast, however, to the lack of recognition and viral escape in the large majority of HLA-B∗27+ patients. Here, we set out to determine the host factors contributing to selective targeting of this epitope.
Methods
Four-digit HLA class I typing and viral sequence analyses were performed in 78 HLA-B∗27+ patients with chronic HCV genotype 1 infection. CD8+ T cell analyses were performed in a subset of patients. In addition, HLA/peptide affinity was compared for HLA-B∗27:02 and 05.
Results
The NS5B2820 epitope is only restricted by the HLA-B∗27 subtype HLA-B∗27:02 (that is frequent in Mediterranean populations), but not by the prototype HLA-B∗27 subtype B∗27:05. Indeed, the epitope is very dominant in HLA-B∗27:02+ patients and is associated with viral escape mutations at the anchor position for HLA-binding in 12 out of 13 HLA-B∗27:02+ chronically infected patients.
Conclusions
The NS5B2820 epitope is immunodominant in the context of HLA-B∗27:02, but is not restricted by other HLA-B∗27 subtypes. This finding suggests an important role of HLA subtypes in the restriction of HCV-specific CD8+ responses. With minor HLA subtypes covering up to 39% of specific populations, these findings may have important implications for the selection of epitopes for global vaccines.
Details
- Title
- HLA-B∗27 subtype specificity determines targeting and viral evolution of a hepatitis C virus-specific CD8+ T cell epitope
- Authors/Creators
- K. Nitschke (Author/Creator) - University of FreiburgA. Barriga (Author/Creator) - Instituto de Salud Carlos IIIJ. Schmidt (Author/Creator) - University of FreiburgJ. Timm (Author/Creator) - University of Duisburg-EssenS. Viazov (Author/Creator) - University of Duisburg-EssenT. Kuntzen (Author/Creator) - Ragon Institute of MGH, MIT and HarvardA.Y. Kim (Author/Creator) - MGH Institute of Health ProfessionsG.M. Lauer (Author/Creator) - MGH Institute of Health ProfessionsT.M. Allen (Author/Creator) - Ragon Institute of MGH, MIT and HarvardS. Gaudieri (Author/Creator) - Murdoch UniversityA. Rauch (Author/Creator) - University Hospital of BernC.M. Lange (Author/Creator) - Goethe University FrankfurtC. Sarrazin (Author/Creator) - Goethe University FrankfurtT. Eiermann (Author/Creator) - Transfusion Medicine, HLA-Laboratory, University Hospital Hamburg-Eppendorf, Hamburg, GermanyJ. Sidney (Author/Creator) - La Jolla Institute for ImmunologyA. Sette (Author/Creator) - La Jolla Institute for ImmunologyR. Thimme (Author/Creator) - University of FreiburgD. López (Author/Creator) - Instituto de Salud Carlos IIIC. Neumann-Haefelin (Author/Creator) - University of Freiburg
- Publication Details
- Journal of Hepatology, Vol.60(1), pp.22-29
- Publisher
- Elsevier
- Identifiers
- 991005540053307891
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
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- Citation topics
- 1 Clinical & Life Sciences
- 1.125 Hepatitis
- 1.125.83 HCV
- Web Of Science research areas
- Gastroenterology & Hepatology
- ESI research areas
- Clinical Medicine