DOI: 10.4049/jimmunol.162.7.4177. Mutations in Immunodominant T Cell Epitopes Derived from the Nonstructural 3 Protein of Hepatitis C Virus Have the Potential for Generating Escape Variants That May Have Important Consequences for T Cell Recognition

Mutations in Immunodominant T Cell Epitopes Derived from the Nonstructural 3 Protein of Hepatitis C Virus Have the Potential for Generating Escape Variants That May Have Important Consequences for T Cell Recognition

10.4049/jimmunol.162.7.4177

Crossref journal-article

Oxford University Press (OUP)

The Journal of Immunology (286)

Abstract

Abstract One of the most disturbing features of hepatitis C virus (HCV) is its long-term persistence in the host. One hypothesis to explain this phenomenon is that HCV escapes immune recognition through its intrinsic hypermutability. To determine whether immunodominant T cell epitopes derived from HCV nonstructural 3 (NS3) protein might be subject to sequence variations leading to escape mutants, we examined sequence variations of one IL-2-producing epitope, NS3358–375, and one IL-10-producing epitope, NS3505–521. By PCR amplification, cloning, and sequencing, we observed significant sequence variations in the two epitopes, although the selection intensity for each epitope was different. For NS3358–375, more variants were observed, and for NS3505–521, fewer mutations were observed. Moreover, functional studies revealed that three NS3358–375 and one NS3505–521 variants failed to stimulate T cell proliferation, and two other NS3358–375 and NS3505–521 variants weakly stimulated T cell responses. Our results are consistent with immune selection of viral variants at the epitope level, which may enable HCV to evade host defenses over time.

Bibliography

Wang, H., & Eckels, D. D. (1999). Mutations in Immunodominant T Cell Epitopes Derived from the Nonstructural 3 Protein of Hepatitis C Virus Have the Potential for Generating Escape Variants That May Have Important Consequences for T Cell Recognition. The Journal of Immunology, 162(7), 4177â4183.

Authors 2

Huiru Wang (first)
David D. Eckels (additional)

References 34 Referenced 73

Dates

Type	When
Created	2 years, 8 months ago (Dec. 31, 2022, 10:20 p.m.)
Deposited	8 months ago (Jan. 2, 2025, 12:28 p.m.)
Indexed	3 months, 4 weeks ago (May 6, 2025, 12:47 a.m.)
Issued	26 years, 5 months ago (April 1, 1999)
Published	26 years, 5 months ago (April 1, 1999)
Published Print	26 years, 5 months ago (April 1, 1999)

Funders 0

None

BibTeX

@article{Wang_1999, title={Mutations in Immunodominant T Cell Epitopes Derived from the Nonstructural 3 Protein of Hepatitis C Virus Have the Potential for Generating Escape Variants That May Have Important Consequences for T Cell Recognition}, volume={162}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.162.7.4177}, DOI={10.4049/jimmunol.162.7.4177}, number={7}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Wang, Huiru and Eckels, David D.}, year={1999}, month=apr, pages={4177–4183} }

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  "abstract": "<jats:title>Abstract</jats:title>\n               <jats:p>One of the most disturbing features of hepatitis C virus (HCV) is its long-term persistence in the host. One hypothesis to explain this phenomenon is that HCV escapes immune recognition through its intrinsic hypermutability. To determine whether immunodominant T cell epitopes derived from HCV nonstructural 3 (NS3) protein might be subject to sequence variations leading to escape mutants, we examined sequence variations of one IL-2-producing epitope, NS3358\u2013375, and one IL-10-producing epitope, NS3505\u2013521. By PCR amplification, cloning, and sequencing, we observed significant sequence variations in the two epitopes, although the selection intensity for each epitope was different. For NS3358\u2013375, more variants were observed, and for NS3505\u2013521, fewer mutations were observed. Moreover, functional studies revealed that three NS3358\u2013375 and one NS3505\u2013521 variants failed to stimulate T cell proliferation, and two other NS3358\u2013375 and NS3505\u2013521 variants weakly stimulated T cell responses. Our results are consistent with immune selection of viral variants at the epitope level, which may enable HCV to evade host defenses over time.</jats:p>",
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