Biomaterial Database

Protective effect of human leukocyte antigen B27 in hepatitis C virus infection requires the presence of a genotype-specific immunodominant CD8+ T-cell epitope. 2010

Christoph Neumann-Haefelin, and Jörg Timm, and Julia Schmidt, and Nadine Kersting, and Karen Fitzmaurice, and Cesar Oniangue-Ndza, and Michael N Kemper, and Isla Humphreys, and Susan McKiernan, and Dermot Kelleher, and Volker Lohmann, and Paul Bowness, and Daniela Huzly, and Hugo R Rosen, and Arthur Y Kim, and Georg M Lauer, and Todd M Allen, and Eleanor Barnes, and Michael Roggendorf, and Hubert E Blum, and Robert Thimme

Department of Medicine II, University of Freiburg, Germany.

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. CONCLUSIONS 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.

UI	MeSH Term	Description	Entries
D006526	Hepatitis C	INFLAMMATION of the LIVER in humans caused by HEPATITIS C VIRUS, a single-stranded RNA virus. Its incubation period is 30-90 days. Hepatitis C is transmitted primarily by contaminated blood parenterally and is often associated with transfusion and intravenous drug abuse. However, in a significant number of cases, the source of hepatitis C infection is unknown.	Hepatitis, Viral, Non-A, Non-B, Parenterally-Transmitted,Parenterally-Transmitted Non-A, Non-B Hepatitis,PT-NANBH,Parenterally Transmitted Non A, Non B Hepatitis
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015796	HLA-B27 Antigen	A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*27 allele family.	HLA Class I Histocompatibility Antigen, B-27 alpha Chain,HLA-B27,Antigen, HLA-B27,HLA B27 Antigen,HLA Class I Histocompatibility Antigen, B 27 alpha Chain
D016056	Immunodominant Epitopes	Subunits of the antigenic determinant that are most easily recognized by the immune system and thus most influence the specificity of the induced antibody.	Antigenic Determinants, Immunodominant,Antigens, Immunodominant,Epitopes, Immunodominant,Immunodominant Determinant,Immunodominant Domain,Immunodominant Epitope,Immunodominant Region,Immunodominant Site,Immunodominant Determinants,Immunodominant Domains,Immunodominant Regions,Immunodominant Sites,Determinant, Immunodominant,Determinants, Immunodominant,Determinants, Immunodominant Antigenic,Domain, Immunodominant,Domains, Immunodominant,Epitope, Immunodominant,Immunodominant Antigenic Determinants,Immunodominant Antigens,Region, Immunodominant,Regions, Immunodominant,Site, Immunodominant,Sites, Immunodominant
D016174	Hepacivirus	A genus of FLAVIVIRIDAE causing parenterally-transmitted HEPATITIS C which is associated with transfusions and drug abuse. Hepatitis C virus is the type species.	Hepatitis C virus,Hepatitis C-Like Viruses,Hepaciviruses,Hepatitis C Like Viruses,Hepatitis C viruses,Hepatitis C-Like Virus
D018414	CD8-Positive T-Lymphocytes	A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.	Suppressor T-Lymphocytes, CD8-Positive,T8 Cells,T8 Lymphocytes,CD8-Positive Lymphocytes,Suppressor T-Cells, CD8-Positive,CD8 Positive Lymphocytes,CD8 Positive T Lymphocytes,CD8-Positive Lymphocyte,CD8-Positive Suppressor T-Cell,CD8-Positive Suppressor T-Cells,CD8-Positive Suppressor T-Lymphocyte,CD8-Positive Suppressor T-Lymphocytes,CD8-Positive T-Lymphocyte,Cell, T8,Cells, T8,Lymphocyte, CD8-Positive,Lymphocyte, T8,Lymphocytes, CD8-Positive,Lymphocytes, T8,Suppressor T Cells, CD8 Positive,Suppressor T Lymphocytes, CD8 Positive,Suppressor T-Cell, CD8-Positive,Suppressor T-Lymphocyte, CD8-Positive,T-Cell, CD8-Positive Suppressor,T-Cells, CD8-Positive Suppressor,T-Lymphocyte, CD8-Positive,T-Lymphocyte, CD8-Positive Suppressor,T-Lymphocytes, CD8-Positive,T-Lymphocytes, CD8-Positive Suppressor,T8 Cell,T8 Lymphocyte
D018984	Epitopes, T-Lymphocyte	Antigenic determinants recognized and bound by the T-cell receptor. Epitopes recognized by the T-cell receptor are often located in the inner, unexposed side of the antigen, and become accessible to the T-cell receptors after proteolytic processing of the antigen.	T-Cell Epitopes,T-Lymphocyte Epitopes,T-Cell Epitope,T-Lymphocyte Epitope,Epitope, T-Cell,Epitope, T-Lymphocyte,Epitopes, T Lymphocyte,Epitopes, T-Cell,T Cell Epitope,T Cell Epitopes,T Lymphocyte Epitope,T Lymphocyte Epitopes