Longitudinal mapping of protective CD4+ T cell responses against HCV: analysis of fluctuating dominant and subdominant HLA-DR11 restricted epitopes

Journal of Viral Hepatitis
G C HarcourtP Klenerman

Abstract

Cellular immunity plays an important role in the control of persistent virus infections such as hepatitis C virus (HCV). Antiviral CD4(+) T cell responses have been shown to accompany resolution of acute disease and there is also a consistent association between HLA Class II genes, notably HLADRB1*1101 (and the closely linked HLADQB1*0301) and disease resolution. We initially mapped longitudinal CD4(+) T cell responses in an individual after spontaneous resolution of acute HCV, and identified three HLA-DR11-restricted responses which vary in immunodominance over time. Functional assays and HLA Class II tetramer staining revealed one to be a response to a commonly recognized epitope, NS3(1248-1261), although cytokine capture assays showed these specific cells to be at a very low frequency. In this patient, and in others reported, this most frequently recognized HLA-DR11 restricted epitope is not immunodominant. We analysed whether sequence variability within and between genotypes might account for differences in recognition of HLA-DR11 restricted epitopes. We found that a limited number, including NS3(1248-1261), showed extreme sequence conservation. Within NS3, the ability of peptides to accept amino acid substitutions was clea...Continue Reading

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Citations

Apr 9, 2011·Biomarkers in Medicine·Julia SchmidtChristoph Neumann-Haefelin
Jul 10, 2008·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Virginia CecconiGiulia Casorati
Apr 9, 2013·PloS One·Steven K HildemannDirk Homann
Feb 20, 2016·Journal of Immunological Methods·Ramgopal R MettuSamuel J Landry
Sep 9, 2005·European Journal of Gastroenterology & Hepatology·Sharon BarrettJohn Crowe
Nov 8, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Thomas J ScribaRodney E Phillips
Sep 9, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Julian Schulze zur WieschBruce D Walker

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