Protective effect of human leukocyte antigen B27 in hepatitis C virus infection requires the presence of a genotype-specific immunodominant CD8+ T-cell epitope.
UNLABELLED: Human leukocyte antigen B27 (HLA-B27) is associated with protection in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection. This protective role is linked to single immunodominant HLA-B27-restricted CD8+ T-cell epitopes in both infections. In order to define the rela...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2010
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| _version_ | 1826269006897610752 |
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| author | Neumann-Haefelin, C Timm, J Schmidt, J Kersting, N Fitzmaurice, K Oniangue-Ndza, C Kemper, M Humphreys, I McKiernan, S Kelleher, D Lohmann, V Bowness, P Huzly, D Rosen, H Kim, A Lauer, G Allen, T Barnes, E Roggendorf, M Blum, H Thimme, R |
| author_facet | Neumann-Haefelin, C Timm, J Schmidt, J Kersting, N Fitzmaurice, K Oniangue-Ndza, C Kemper, M Humphreys, I McKiernan, S Kelleher, D Lohmann, V Bowness, P Huzly, D Rosen, H Kim, A Lauer, G Allen, T Barnes, E Roggendorf, M Blum, H Thimme, R |
| author_sort | Neumann-Haefelin, C |
| collection | OXFORD |
| description | UNLABELLED: Human leukocyte antigen B27 (HLA-B27) is associated with protection in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection. This protective role is linked to single immunodominant HLA-B27-restricted CD8+ T-cell epitopes in both infections. In order to define the relative contribution of a specific HLA-B27-restricted epitope to the natural course of HCV infection, we compared the biological impact of the highly conserved HCV genotype 1 epitope, for which the protective role has been described, with the corresponding region in genotype 3 that differs in its sequence by three amino acid residues. The genotype 3a peptide was not recognized by CD8+ T cells specific for the genotype 1 peptide. Furthermore, patients with acute or chronic infection with HCV genotype 3a did not mount T-cell responses to this epitope region, and their autologous viral sequences showed no evidence of T-cell pressure. Finally, we found a significantly higher frequency of HLA-B27 positivity in patients with chronic HCV genotype 3a infection compared to genotype 1 infection, indicating that there is no protection by HLA-B27 in HCV genotype 3 infection. CONCLUSION: Our data indicate that the protective effect of HLA-B27 is limited to HCV genotype 1 infection and does not expand to other genotypes such as genotype 3a. This can most likely be explained by intergenotype sequence diversity leading to the loss of the immunodominant HLA-B27 epitope in viral strains other than genotype 1. Our results underline the central role of a single HLA-B27-restricted epitope-specific CD8+ T-cell response in mediating protection in HCV genotype 1 infection. |
| first_indexed | 2024-03-06T21:18:17Z |
| format | Journal article |
| id | oxford-uuid:408c0c9d-8f33-4c80-b9aa-c5ad245aaca7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:18:17Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:408c0c9d-8f33-4c80-b9aa-c5ad245aaca72022-03-26T14:38:35ZProtective effect of human leukocyte antigen B27 in hepatitis C virus infection requires the presence of a genotype-specific immunodominant CD8+ T-cell epitope.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:408c0c9d-8f33-4c80-b9aa-c5ad245aaca7EnglishSymplectic Elements at Oxford2010Neumann-Haefelin, CTimm, JSchmidt, JKersting, NFitzmaurice, KOniangue-Ndza, CKemper, MHumphreys, IMcKiernan, SKelleher, DLohmann, VBowness, PHuzly, DRosen, HKim, ALauer, GAllen, TBarnes, ERoggendorf, MBlum, HThimme, RUNLABELLED: Human leukocyte antigen B27 (HLA-B27) is associated with protection in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection. This protective role is linked to single immunodominant HLA-B27-restricted CD8+ T-cell epitopes in both infections. In order to define the relative contribution of a specific HLA-B27-restricted epitope to the natural course of HCV infection, we compared the biological impact of the highly conserved HCV genotype 1 epitope, for which the protective role has been described, with the corresponding region in genotype 3 that differs in its sequence by three amino acid residues. The genotype 3a peptide was not recognized by CD8+ T cells specific for the genotype 1 peptide. Furthermore, patients with acute or chronic infection with HCV genotype 3a did not mount T-cell responses to this epitope region, and their autologous viral sequences showed no evidence of T-cell pressure. Finally, we found a significantly higher frequency of HLA-B27 positivity in patients with chronic HCV genotype 3a infection compared to genotype 1 infection, indicating that there is no protection by HLA-B27 in HCV genotype 3 infection. CONCLUSION: Our data indicate that the protective effect of HLA-B27 is limited to HCV genotype 1 infection and does not expand to other genotypes such as genotype 3a. This can most likely be explained by intergenotype sequence diversity leading to the loss of the immunodominant HLA-B27 epitope in viral strains other than genotype 1. Our results underline the central role of a single HLA-B27-restricted epitope-specific CD8+ T-cell response in mediating protection in HCV genotype 1 infection. |
| spellingShingle | Neumann-Haefelin, C Timm, J Schmidt, J Kersting, N Fitzmaurice, K Oniangue-Ndza, C Kemper, M Humphreys, I McKiernan, S Kelleher, D Lohmann, V Bowness, P Huzly, D Rosen, H Kim, A Lauer, G Allen, T Barnes, E Roggendorf, M Blum, H Thimme, R Protective effect of human leukocyte antigen B27 in hepatitis C virus infection requires the presence of a genotype-specific immunodominant CD8+ T-cell epitope. |
| title | Protective effect of human leukocyte antigen B27 in hepatitis C virus infection requires the presence of a genotype-specific immunodominant CD8+ T-cell epitope. |
| title_full | Protective effect of human leukocyte antigen B27 in hepatitis C virus infection requires the presence of a genotype-specific immunodominant CD8+ T-cell epitope. |
| title_fullStr | Protective effect of human leukocyte antigen B27 in hepatitis C virus infection requires the presence of a genotype-specific immunodominant CD8+ T-cell epitope. |
| title_full_unstemmed | Protective effect of human leukocyte antigen B27 in hepatitis C virus infection requires the presence of a genotype-specific immunodominant CD8+ T-cell epitope. |
| title_short | Protective effect of human leukocyte antigen B27 in hepatitis C virus infection requires the presence of a genotype-specific immunodominant CD8+ T-cell epitope. |
| title_sort | protective effect of human leukocyte antigen b27 in hepatitis c virus infection requires the presence of a genotype specific immunodominant cd8 t cell epitope |
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