Cytotoxic T lymphocyte response to hepatitis C virus-derived peptides containing the HLA A2.1 binding motif - PubMed (original) (raw)
Cytotoxic T lymphocyte response to hepatitis C virus-derived peptides containing the HLA A2.1 binding motif
A Cerny et al. J Clin Invest. 1995 Feb.
Abstract
The HLA class I-restricted cytotoxic T lymphocyte (CTL) response is a major defense mechanism in viral infections. It has been suggested that the CTL response may contribute to viral clearance and liver cell injury during hepatitis C virus (HCV) infection. To test this hypothesis requires an understanding of the characteristics of HCV-specific cytotoxic effector cells and identification of the target antigens to which they respond. To begin this process we stimulated peripheral blood mononuclear cells (PBMC) from a group of HLA-A2 positive patients with chronic hepatitis C with a panel of 130 HCV-derived peptides containing the HLA-A2 binding motif. Effector cells were tested for their capacity to lyse HLA-A2-matched target cells that were either sensitized with peptide or infected with a vaccinia virus construct containing HCV sequences. Using this approach we have identified nine immunogenic peptides in HCV, three of which are derived from the putative core protein, three from the nonstructural (NS) 3 domain, two from NS4 and one from NS5. Selected responses were shown to be HLA-A2 restricted, mediated by CD8+ T cells and to recognize endogenously synthesized viral antigen. Unexpectedly, peptide-specific CTL responses could also be induced in sero-negative individuals, suggesting in vitro activation of naive CTL precursors. The precursor frequency of peptide-specific CTL was 10 to 100-fold higher in infected patients compared to uninfected controls, and the responses were greatly diminished by removal of CD45 RO+ (memory) T cells. Further quantitative studies are clearly required to establish whether a correlation exists between the HCV-specific CTL response and the clinical course of this disease. Definition of the molecular targets of the human CTL response to HCV creates this opportunity, and may also contribute to the development of a T cell-based HCV vaccine.
Similar articles
- CTL responses of HLA-A2.1-transgenic mice specific for hepatitis C viral peptides predict epitopes for CTL of humans carrying HLA-A2.1.
Shirai M, Arichi T, Nishioka M, Nomura T, Ikeda K, Kawanishi K, Engelhard VH, Feinstone SM, Berzofsky JA. Shirai M, et al. J Immunol. 1995 Mar 15;154(6):2733-42. J Immunol. 1995. PMID: 7533182 - Patients with chronic hepatitis C have circulating cytotoxic T cells which recognize hepatitis C virus-encoded peptides binding to HLA-A2.1 molecules.
Battegay M, Fikes J, Di Bisceglie AM, Wentworth PA, Sette A, Celis E, Ching WM, Grakoui A, Rice CM, Kurokohchi K, et al. Battegay M, et al. J Virol. 1995 Apr;69(4):2462-70. doi: 10.1128/JVI.69.4.2462-2470.1995. J Virol. 1995. PMID: 7884894 Free PMC article. - HLA A2 restricted cytotoxic T lymphocyte responses to multiple hepatitis B surface antigen epitopes during hepatitis B virus infection.
Nayersina R, Fowler P, Guilhot S, Missale G, Cerny A, Schlicht HJ, Vitiello A, Chesnut R, Person JL, Redeker AG, Chisari FV. Nayersina R, et al. J Immunol. 1993 May 15;150(10):4659-71. J Immunol. 1993. PMID: 7683326 - Characteristics of the intrahepatic cytotoxic T lymphocyte response in chronic hepatitis C virus infection.
Koziel MJ, Walker BD. Koziel MJ, et al. Springer Semin Immunopathol. 1997;19(1):69-83. doi: 10.1007/BF00945026. Springer Semin Immunopathol. 1997. PMID: 9266632 Review. - T cell recognition of hepatitis B and C viral antigens.
Jung MC, Diepolder HM, Pape GR. Jung MC, et al. Eur J Clin Invest. 1994 Oct;24(10):641-50. doi: 10.1111/j.1365-2362.1994.tb01055.x. Eur J Clin Invest. 1994. PMID: 7531642 Review.
Cited by
- Inflammation and Liver Cell Death in Patients with Hepatitis C Viral Infection.
Neuman MG, Cohen LB. Neuman MG, et al. Curr Issues Mol Biol. 2021 Nov 16;43(3):2022-2035. doi: 10.3390/cimb43030139. Curr Issues Mol Biol. 2021. PMID: 34889885 Free PMC article. - Dissection of two drug-targeted regions of Hepatitis C virus subtype 4a infecting Egyptian patients.
El-Tahan RR, Ghoneim AM, Zaghloul H. El-Tahan RR, et al. Virus Genes. 2020 Oct;56(5):564-581. doi: 10.1007/s11262-020-01776-y. Epub 2020 Jun 22. Virus Genes. 2020. PMID: 32572756 Free PMC article. - Evidence of CD4+ T cell-mediated immune pressure on the Hepatitis C virus genome.
Lucas M, Deshpande P, James I, Rauch A, Pfafferott K, Gaylard E, Merani S, Plauzolles A, Lucas A, McDonnell W, Kalams S, Pilkinton M, Chastain C, Barnett L, Prosser A, Mallal S, Fitzmaurice K, Drummer H, Ansari MA, Pedergnana V, Barnes E, John M, Kelleher D, Klenerman P, Gaudieri S. Lucas M, et al. Sci Rep. 2018 May 8;8(1):7224. doi: 10.1038/s41598-018-25559-6. Sci Rep. 2018. PMID: 29740042 Free PMC article. - Functional differences in hepatitis C virus nonstructural (NS) 3/4A- and 5A-specific T cell responses.
Holmström F, Chen M, Balasiddaiah A, Sällberg M, Ahlén G, Frelin L. Holmström F, et al. Sci Rep. 2016 May 4;6:24991. doi: 10.1038/srep24991. Sci Rep. 2016. PMID: 27141891 Free PMC article. - A Novel Adeno-Associated Virus-Based Genetic Vaccine Encoding the Hepatitis C Virus NS3/4 Protein Exhibits Immunogenic Properties in Mice Superior to Those of an NS3-Protein-Based Vaccine.
Zhu F, Chen T, Zhang Y, Sun H, Cao H, Lu J, Zhao L, Li G. Zhu F, et al. PLoS One. 2015 Nov 10;10(11):e0142349. doi: 10.1371/journal.pone.0142349. eCollection 2015. PLoS One. 2015. PMID: 26556235 Free PMC article.
References
- Virology. 1992 Jun;188(2):819-30 - PubMed
- Curr Stud Hematol Blood Transfus. 1994;(61):12-35 - PubMed
- J Immunol. 1986 Apr 1;136(7):2348-57 - PubMed
- Mol Cell Biol. 1985 Dec;5(12):3403-9 - PubMed
- J Exp Med. 1986 Oct 1;164(4):1075-92 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous