Detection of a Broad Range of Low-Level Major Histocompatibility Complex Class II-Restricted, Hepatitis Delta Virus (HDV)-Specific T-Cell Responses Regardless of Clinical Status
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Detection of a Broad Range of Low-Level Major Histocompatibility Complex Class II-Restricted, Hepatitis Delta Virus (HDV)-Specific T-Cell Responses Regardless of Clinical Status. / Landahl, Johanna; Bockmann, Jan Hendrik; Scheurich, Christoph; Ackermann, Christin; Matzat, Verena; Heide, Janna; Nuurei, Tungalag; D'Antonio, Gianluca; von Felden, Johann; Sette, Alessandro; Peine, Sven; Lohse, Ansgar W; Lütgehetmann, Marc; Marget, Matthias; Sidney, John; Schulze Zur Wiesch, Julian.
In: J INFECT DIS, Vol. 219, No. 4, 29.01.2019, p. 568-577.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Detection of a Broad Range of Low-Level Major Histocompatibility Complex Class II-Restricted, Hepatitis Delta Virus (HDV)-Specific T-Cell Responses Regardless of Clinical Status
AU - Landahl, Johanna
AU - Bockmann, Jan Hendrik
AU - Scheurich, Christoph
AU - Ackermann, Christin
AU - Matzat, Verena
AU - Heide, Janna
AU - Nuurei, Tungalag
AU - D'Antonio, Gianluca
AU - von Felden, Johann
AU - Sette, Alessandro
AU - Peine, Sven
AU - Lohse, Ansgar W
AU - Lütgehetmann, Marc
AU - Marget, Matthias
AU - Sidney, John
AU - Schulze Zur Wiesch, Julian
PY - 2019/1/29
Y1 - 2019/1/29
N2 - Background: This study aimed to comprehensively define the breadth and specificity of the hepatitis delta virus (HDV)-specific T-cell response in patients at different stages of chronic coinfection with hepatitis B virus (HBV).Methods: Following in vitro stimulation with an overlapping set of 21 HDV-specific 20mer peptides and exogenous interleukin 2, HDV-specific CD4+ and CD8+ T-cell responses of 32 HDV-infected patients were analyzed by enzyme-linked immunospot analysis and intracellular cytokine staining for interferon γ production at the single-peptide level. Additionally, HLA-binding studies were performed both in silico and in vitro.Results: We were able to detect ≥1 T-cell response in >50% our patients. Interestingly, there was no significant difference between the breadth of the response in patients positive and those negative for HDV by PCR. HDV-specific T-cell responses focused on 3 distinct HDV-specific epitopes that were each detected in 12%-21% of patients-2 HLA class II-restricted epitopes (amino acids 11-30 and 41-60) and 1 major histocompatibility complex class I-restricted epitope (amino acids 191-210). In in vitro HLA-binding assays, the 2 CD4+ T-cell specificities (amino acids 11-30 and 41-60) showed promiscuous binding to multiple HLA-DR molecules.Conclusions: This comprehensive characterization of HDV T-cell epitopes provides important information that will facilitate further studies of HDV immunopathogenesis.
AB - Background: This study aimed to comprehensively define the breadth and specificity of the hepatitis delta virus (HDV)-specific T-cell response in patients at different stages of chronic coinfection with hepatitis B virus (HBV).Methods: Following in vitro stimulation with an overlapping set of 21 HDV-specific 20mer peptides and exogenous interleukin 2, HDV-specific CD4+ and CD8+ T-cell responses of 32 HDV-infected patients were analyzed by enzyme-linked immunospot analysis and intracellular cytokine staining for interferon γ production at the single-peptide level. Additionally, HLA-binding studies were performed both in silico and in vitro.Results: We were able to detect ≥1 T-cell response in >50% our patients. Interestingly, there was no significant difference between the breadth of the response in patients positive and those negative for HDV by PCR. HDV-specific T-cell responses focused on 3 distinct HDV-specific epitopes that were each detected in 12%-21% of patients-2 HLA class II-restricted epitopes (amino acids 11-30 and 41-60) and 1 major histocompatibility complex class I-restricted epitope (amino acids 191-210). In in vitro HLA-binding assays, the 2 CD4+ T-cell specificities (amino acids 11-30 and 41-60) showed promiscuous binding to multiple HLA-DR molecules.Conclusions: This comprehensive characterization of HDV T-cell epitopes provides important information that will facilitate further studies of HDV immunopathogenesis.
KW - Journal Article
U2 - 10.1093/infdis/jiy549
DO - 10.1093/infdis/jiy549
M3 - SCORING: Journal article
C2 - 30247653
VL - 219
SP - 568
EP - 577
JO - J INFECT DIS
JF - J INFECT DIS
SN - 0022-1899
IS - 4
ER -