Immunogenicity of twenty peptides representing epitopes of the hepatitis B core and surface antigens by IFN-γ response in chronic and resolved HBVReportar como inadecuado

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BMC Immunology

, 16:65

Cellular Immunology and immune regulation


BackgroundPatients with chronic hepatitis B virus infection CHB usually mount a modest T cell response against HBV epitopes. In order to determine immunogenic epitopes of HBV recognized by HBV-specific T cells, previous studies focused on previously confirmed HBV epitopes and assessed the T cell response by the number of HBV-specific T cells by IFN-γ ELISPOT.

MethodsWe studied T cell functionality by combined in silico methods predicting HBV-specific epitopes and experimental investigations on the recognition of these epitopes. 30 chronic CHB patients and 10 patients with resolved HBV RHB were included in the study. We identified epitopes from the literature and by in silico analysis. These were evaluated for immunogenicity by use of synthetic peptides representing the epitopes through exposure to PBMCs from patients with CHB or RHB by IFN-γ ELISPOT. The number of IFN-γ producing cells SFC, mean spot size MSS and stimulation index SI were recorded.

ResultsThe frequency of HBV-specific T cells producing IFN-γ after stimulation with HBV epitopes was similar in CHB and RHB patients. CHB patients had a higher MSS SI than RHB patients. Patients not carrying the HLA-A2 genotype had higher SFC SI and MSS SI. Patients with HLA-A11 had higher MSS SI compared to non- HLA-A11 allele patients. HBeAg-positive patients had a lower MSS SI, and none of the HBeAg positive patients had the HLA-A11 genotype. We found 3 immunogenic epitopes not described previously.

ConclusionIFN-γ ELISPOT-determined MSS is an efficient marker for T cell recognition of epitopes. This experimental measure showed the in silico analysis for epitope prediction to be a valuable tool in future studies on HLA genotypes and HBV epitopes. This way our study now points to previously unappreciated consequences of carrying the HLA-A11 allele in terms of stronger immunity to HBV.

KeywordsHepatitis B virus T cell immunity HLA genotypes IFN-γ ELISPOT Epitope prediction AbbreviationsHBVHepatitis B Virus infection

IL-10Interleukin 10

PD-L1Programmed cell Death Ligand 1

CTLCytotoxic T lymphocytes

KDDissociation constant

MHCMajor Histocompability Complex

IFN-γInterferon gamma

ELISPOTEnzyme-linked immunosorbent spot

CHBChronic Hepatitis B Virus infection

RHBResolved Hepatitis B Virus infection

HBsAgHepatitis B virus s-antigen

HBcAgHepatitis B virus c-antigen

HIVHuman ImmunodeficiencyVirus

HCVHepatitis C Virus infection

HBeAgHepatitis B virus e-antigen

anti-HBeAntibodies against HBeAg

anti-HBcAntibodies against HBcAg

anti-HBsAntibodies against HBsAg

ELISAEnzyme-linked immunosorbent assay

HBV DNAHepatitis B Virus deoxyribonucleic acid

PBMCPeripheral Blood Mononuclear Blood Cells

PBSPhosphate Buffered Saline

FCSFetal Calf Serum

DMSODimethyl Sulfoxid

PCRPolymerase Chain Reaction

AEC3-amino-9-ethyl carbazole

SFCSpot Forming Cell IFN-y producing cell

MSSMean Spot Size

SIStimulation Index

ANOVAAnalysis of Variance

ECExperimentally Confirmed

CPComputer Predictions

AUCArea Under the Curve

APCAntigen Presenting Cells

TCMCentral Memory T cells

TEMEffector Memory T cells

CCR7C-C chemokine Receptor type 7

IL-7Interleukin 7

CD127alpha-chain of the IL-7 receptor

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Autor: Nanna-Sophie Brinck-Jensen - Thomas Vorup-Jensen - Peter Derek Christian Leutscher - Christian Erikstrup - Eskild Petersen


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