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HLA-B*27 subtype specificity determines targeting and viral evolution of a hepatitis C virus-specific CD8+ T cell epitope

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HLA-B*27 subtype specificity determines targeting and viral evolution of a hepatitis C virus-specific CD8+ T cell epitope. / Nitschke, Katja; Barriga, Alejandro; Schmidt, Julia; Timm, Jörg; Viazov, Sergei; Kuntzen, Thomas; Kim, Arthur Y; Lauer, Georg M; Allen, Todd M; Gaudieri, Silvana; Rauch, Andri; Lange, Christian M; Sarrazin, Christoph; Eiermann, Thomas; Sidney, John; Sette, Alessandro; Thimme, Robert; López, Daniel; Neumann-Haefelin, Christoph.

in: J HEPATOL, Jahrgang 60, Nr. 1, 01.01.2014, S. 22-29.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Nitschke, K, Barriga, A, Schmidt, J, Timm, J, Viazov, S, Kuntzen, T, Kim, AY, Lauer, GM, Allen, TM, Gaudieri, S, Rauch, A, Lange, CM, Sarrazin, C, Eiermann, T, Sidney, J, Sette, A, Thimme, R, López, D & Neumann-Haefelin, C 2014, 'HLA-B*27 subtype specificity determines targeting and viral evolution of a hepatitis C virus-specific CD8+ T cell epitope', J HEPATOL, Jg. 60, Nr. 1, S. 22-29. https://doi.org/10.1016/j.jhep.2013.08.009

APA

Nitschke, K., Barriga, A., Schmidt, J., Timm, J., Viazov, S., Kuntzen, T., Kim, A. Y., Lauer, G. M., Allen, T. M., Gaudieri, S., Rauch, A., Lange, C. M., Sarrazin, C., Eiermann, T., Sidney, J., Sette, A., Thimme, R., López, D., & Neumann-Haefelin, C. (2014). HLA-B*27 subtype specificity determines targeting and viral evolution of a hepatitis C virus-specific CD8+ T cell epitope. J HEPATOL, 60(1), 22-29. https://doi.org/10.1016/j.jhep.2013.08.009

Vancouver

Nitschke K, Barriga A, Schmidt J, Timm J, Viazov S, Kuntzen T et al. HLA-B*27 subtype specificity determines targeting and viral evolution of a hepatitis C virus-specific CD8+ T cell epitope. J HEPATOL. 2014 Jan 1;60(1):22-29. https://doi.org/10.1016/j.jhep.2013.08.009

Bibtex

@article{8f3aa77a8339484bbe00cd2488f4c6db,
title = "HLA-B*27 subtype specificity determines targeting and viral evolution of a hepatitis C virus-specific CD8+ T cell epitope",
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.",
keywords = "CD8-Positive T-Lymphocytes, Epitopes, T-Lymphocyte, HLA-B27 Antigen, Hepacivirus, Humans, Viral Nonstructural Proteins",
author = "Katja Nitschke and Alejandro Barriga and Julia Schmidt and J{\"o}rg Timm and Sergei Viazov and Thomas Kuntzen and Kim, {Arthur Y} and Lauer, {Georg M} and Allen, {Todd M} and Silvana Gaudieri and Andri Rauch and Lange, {Christian M} and Christoph Sarrazin and Thomas Eiermann and John Sidney and Alessandro Sette and Robert Thimme and Daniel L{\'o}pez and Christoph Neumann-Haefelin",
note = "Copyright {\textcopyright} 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.",
year = "2014",
month = jan,
day = "1",
doi = "10.1016/j.jhep.2013.08.009",
language = "English",
volume = "60",
pages = "22--29",
journal = "J HEPATOL",
issn = "0168-8278",
publisher = "Elsevier",
number = "1",

}

RIS

TY - JOUR

T1 - HLA-B*27 subtype specificity determines targeting and viral evolution of a hepatitis C virus-specific CD8+ T cell epitope

AU - Nitschke, Katja

AU - Barriga, Alejandro

AU - Schmidt, Julia

AU - Timm, Jörg

AU - Viazov, Sergei

AU - Kuntzen, Thomas

AU - Kim, Arthur Y

AU - Lauer, Georg M

AU - Allen, Todd M

AU - Gaudieri, Silvana

AU - Rauch, Andri

AU - Lange, Christian M

AU - Sarrazin, Christoph

AU - Eiermann, Thomas

AU - Sidney, John

AU - Sette, Alessandro

AU - Thimme, Robert

AU - López, Daniel

AU - Neumann-Haefelin, Christoph

N1 - Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

KW - CD8-Positive T-Lymphocytes

KW - Epitopes, T-Lymphocyte

KW - HLA-B27 Antigen

KW - Hepacivirus

KW - Humans

KW - Viral Nonstructural Proteins

U2 - 10.1016/j.jhep.2013.08.009

DO - 10.1016/j.jhep.2013.08.009

M3 - SCORING: Journal article

C2 - 23978718

VL - 60

SP - 22

EP - 29

JO - J HEPATOL

JF - J HEPATOL

SN - 0168-8278

IS - 1

ER -