Synergism of tapasin and human leukocyte antigens in resolving hepatitis C virus infection

Ashraf, S. et al. (2013) Synergism of tapasin and human leukocyte antigens in resolving hepatitis C virus infection. Hepatology, 58(3), pp. 881-889. (doi: 10.1002/hep.26415) (PMID:23532923) (PMCID:PMC3759612)

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Abstract

CD8+ T‐cell responses to hepatitis C virus (HCV) are important in generating a successful immune response and spontaneously clearing infection. Human leukocyte antigen (HLA) class I presents viral peptides to CD8+ T cells to permit detection of infected cells, and tapasin is an important component of the peptide loading complex for HLA class I. We sought to determine if tapasin polymorphisms affected the outcome of HCV infection. Patients with resolved or chronic HCV infection were genotyped for the known G/C coding polymorphism in exon 4 of the tapasin gene. In a European, but not a US, Caucasian population, the tapasin G allele was significantly associated with the outcome of HCV infection, being found in 82.5% of resolvers versus 71.3% of persistently infected individuals (P = 0.02, odds ratio [OR] = 1.90 95% confidence interval [CI] = 1.11‐3.23). This was more marked at the HLA‐B locus at which heterozygosity of both tapasin and HLA‐B was protective (P < 0.03). Individuals with an HLA‐B allele with an aspartate at residue 114 and the tapasin G allele were more likely to spontaneously resolve HCV infection (P < 0.00003, OR = 3.2 95% CI = 1.6‐6.6). Additionally, individuals with chronic HCV and the combination of an HLA‐B allele with an aspartate at residue 114 and the tapasin G allele also had stronger CD8+ T‐cell responses (P = 0.02, OR = 2.58, 95% CI‐1.05‐6.5). Conclusion: Tapasin alleles contribute to the outcome of HCV infection by synergizing with polymorphisms at HLA‐B in a population‐specific manner. This polymorphism may be relevant for peptide vaccination strategies against HCV infection.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ashraf, Dr Shirin
Authors: Ashraf, S., Nitschke, K., Warshow, U. M., Brooks, C. R., Kim, A. Y., Lauer, G. M., Hydes, T. J., Cramp, M. E., Alexander, G., Little, A.-M., Thimme, R., Neumann-Haefelin, C., and Khakoo, S. I.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Hepatology
Publisher:Wiley
ISSN:0270-9139
ISSN (Online):1527-3350
Published Online:26 March 2013
Copyright Holders:Copyright © 2013 American Association for the Study of Liver Diseases
First Published:First published in Hepatology 58(3): 881-889
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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