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

Synergism of tapasin and human leukocyte antigens in resolving hepatitis C virus infection
Synergism of tapasin and human leukocyte antigens in resolving hepatitis C virus infection
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.
0270-9139
881-889
Ashraf, Shirin
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Nitschke, Katja
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Warshow, Usama M.
f7a9686a-0bf4-4fe1-80d0-ca69bf5e7eaf
Brooks, Collin R.
a9ae35ca-98a6-4e01-8336-859c98424b11
Kim, Arthur Y.
c1677b18-8300-4e04-b0d1-8636b66c8ff8
Lauer, Georg M.
e7217e36-9234-4134-9c18-e95da7fb4a4a
Hydes, Theresa J.
c7744323-57ce-48fd-be8d-e299554297d9
Cramp, Matthew E.
94034caa-fd63-48ef-bb7f-8f02f833bbce
Alexander, Graeme
d6f9e2a6-e860-4de0-9266-a6b12a1c55e5
Little, Ann-Margaret
1ad746bc-64f8-4a63-b067-288cf20c9c87
Thimme, Robert
93843c48-556e-4ab6-bade-5e7155974543
Neumann-Haefelin, Christoph
e8f353b6-4f7a-4284-8e88-83305506d45b
Khakoo, Salim I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273
Ashraf, Shirin
15f24f8c-b2aa-422a-a7a4-e1189ea57ea0
Nitschke, Katja
3c32a1b1-18fb-421e-91fd-73ab28a3cf0b
Warshow, Usama M.
f7a9686a-0bf4-4fe1-80d0-ca69bf5e7eaf
Brooks, Collin R.
a9ae35ca-98a6-4e01-8336-859c98424b11
Kim, Arthur Y.
c1677b18-8300-4e04-b0d1-8636b66c8ff8
Lauer, Georg M.
e7217e36-9234-4134-9c18-e95da7fb4a4a
Hydes, Theresa J.
c7744323-57ce-48fd-be8d-e299554297d9
Cramp, Matthew E.
94034caa-fd63-48ef-bb7f-8f02f833bbce
Alexander, Graeme
d6f9e2a6-e860-4de0-9266-a6b12a1c55e5
Little, Ann-Margaret
1ad746bc-64f8-4a63-b067-288cf20c9c87
Thimme, Robert
93843c48-556e-4ab6-bade-5e7155974543
Neumann-Haefelin, Christoph
e8f353b6-4f7a-4284-8e88-83305506d45b
Khakoo, Salim I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273

Ashraf, Shirin, Nitschke, Katja, Warshow, Usama M., Brooks, Collin R., Kim, Arthur Y., Lauer, Georg M., Hydes, Theresa J., Cramp, Matthew E., Alexander, Graeme, Little, Ann-Margaret, Thimme, Robert, Neumann-Haefelin, Christoph and Khakoo, Salim I. (2013) Synergism of tapasin and human leukocyte antigens in resolving hepatitis C virus infection. Hepatology, 58 (3), 881-889. (doi:10.1002/hep.26415). (PMID:23532923)

Record type: Article

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.

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e-pub ahead of print date: 29 July 2013
Published date: September 2013
Organisations: Clinical & Experimental Sciences

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Local EPrints ID: 356242
URI: https://eprints.soton.ac.uk/id/eprint/356242
ISSN: 0270-9139
PURE UUID: 2fcc1fa6-d77c-4d20-ae97-7812b2ade0b7

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Date deposited: 17 Sep 2013 11:12
Last modified: 18 Jul 2017 03:40

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Contributors

Author: Shirin Ashraf
Author: Katja Nitschke
Author: Usama M. Warshow
Author: Collin R. Brooks
Author: Arthur Y. Kim
Author: Georg M. Lauer
Author: Theresa J. Hydes
Author: Matthew E. Cramp
Author: Graeme Alexander
Author: Ann-Margaret Little
Author: Robert Thimme
Author: Christoph Neumann-Haefelin
Author: Salim I. Khakoo

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