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.
J Infect Dis
; 219(4): 568-577, 2019 01 29.
Article
em En
| MEDLINE
| ID: mdl-30247653
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hepatite D
/
Vírus Delta da Hepatite
/
Linfócitos T
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Antígenos de Histocompatibilidade Classe II
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Epitopos de Linfócito T
/
Hepatite B Crônica
Tipo de estudo:
Diagnostic_studies
Limite:
Adult
/
Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article