[A HLA-A2-restricted-CTL epitope variation at the N-terminal of HCV helicase and the immune response of CTLs].

Abstract

AIM:

To investigate a HLA-A2-restricted CTL epitope variation at the N terminal of hepatitis C virus (HCV) helicase and the proliferative response of cytotoxic T lymphocytes (CTLs) to this epitope.

METHODS:

Two patients infected with HCV were followed up for 7 years. Blood samples taken at the first year and the fifth year were used for viral RNA extraction. Using RT-PCR, the N terminal gene of helicase region was amplified from the extracted RNA. The amplified segments were subcloned and sequenced to assess the epitope variation. A HLA-A2-restricted CTL epitope peptide was synthesized according to the sequencing result. HLA types of the two patients were determined by serological method. The peripheral blood lymphocytes were separated from the two patients at 7th year after infection and cultured with the synthetic CTL epitope peptide to assess the CTL's proliferative response.

RESULTS:

In the HLA-A2(+) individual, there was an amber mutation at the first amino acid of the epitope in the first year after infection, but the amber mutation disappeared after 5 years. However, in the HLA-A2(-) individual, the epitope had neither variation nor amber mutation in 5 years after infection. 7 years after HCV infection, T lymphocytes from both individuals had no proliferative response to the epitope peptide.

CONCLUSION:

The amber mutation of the epitope at N terminal of helicase may be associated with viral immune escape. CTLs have no response to the epitope peptide in the N terminal of HCV helicase in the later stage of chronic HCV infection.

• Authors: Hua-zhang Guo, Wen-liang Wang, Tao Wang
• Journal: Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology (Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi) Vol. 20 Issue 3 Pg. 325-7 (May 2004) ISSN: 1007-8738 [Print] China
• PMID: 15193229 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Epitopes, T-Lymphocyte
• HLA-A2 Antigen
• NS3 protein, hepatitis C virus
• RNA, Viral
• Viral Nonstructural Proteins
• RNA Helicases

Topics

• Adult
• Amino Acid Sequence
• Epitopes, T-Lymphocyte (genetics, immunology)
• Genetic Variation
• HLA-A2 Antigen (analysis)
• Hepacivirus (enzymology, genetics, immunology)
• Hepatitis C (genetics, immunology, virology)
• Humans
• Male
• Molecular Sequence Data
• RNA Helicases (genetics, immunology)
• RNA, Viral (analysis)
• T-Lymphocytes, Cytotoxic (immunology)
• Viral Nonstructural Proteins (genetics, immunology)