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Hypervariable region 1 variant acting as TCR antagonist affects hepatitis C virus-specific CD4+ T cell repertoire by favoring CD95-mediated apoptosis.

Publication ,  Journal Article
Scottà, C; Tuosto, L; Masci, AM; Racioppi, L; Piccolella, E; Frasca, L
Published in: J Leukoc Biol
August 2005

We have described previously that hypervariable region 1 (HVR1) variants of hepatitis C virus (HCV) frequently act as T cell receptor (TCR) antagonists for HVR1-specific helper T cells. These naturally occurring HVR1-antagonistic sequences interfered with the effects of HVR1-agonistic sequences such as TCR down-regulation and early activatory signals. By taking advantage of these findings, in this paper, we have analyzed the fate of these HVR1-specific antagonized CD4+ T cells. We present the evidence that TCR antagonism renders agonist-activated T cells susceptible to bystander CD95-mediated killing by suppressing the expression of cellular Fas-associated death domain-like interleukin-1beta-converting enzyme-like inhibitor proteins. To verify whether the TCR repertoire of a HVR1-specific T cell population could be modified consequently, we used a HVR1-agonistic sequence to induce in vitro CD4+ T cells and another HVR1 sequence with antagonistic property to mediate suppressive phenomena. HVR1-specific T cells were cultured with the agonist alone or with the agonist plus the antagonist. HVR1 specificity and T cell repertoires were followed over time by analyzing TCR beta-variable gene segment by "spectratyping". The results showed that the specificity for the agonist was rapidly spoiled after culture in the presence of the antagonist, and the TCR repertoire was strongly modified as a result of CD95-mediated apoptosis of agonist-specific clonal expansions. These data support the hypothesis that in HCV infection, the generation of TCR antagonists may reshape the T cell repertoire, representing an efficacious immune evasion strategy of a highly mutant pathogen.

Duke Scholars

Published In

J Leukoc Biol

DOI

ISSN

0741-5400

Publication Date

August 2005

Volume

78

Issue

2

Start / End Page

372 / 382

Location

England

Related Subject Headings

  • fas Receptor
  • Viral Proteins
  • T-Lymphocyte Subsets
  • Serpins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Lymphocyte Activation
  • Immunology
  • Humans
  • Hepacivirus
  • Epitopes, T-Lymphocyte
 

Citation

APA
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MLA
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Scottà, C., Tuosto, L., Masci, A. M., Racioppi, L., Piccolella, E., & Frasca, L. (2005). Hypervariable region 1 variant acting as TCR antagonist affects hepatitis C virus-specific CD4+ T cell repertoire by favoring CD95-mediated apoptosis. J Leukoc Biol, 78(2), 372–382. https://doi.org/10.1189/jlb.0804456
Scottà, Cristiano, Loretta Tuosto, Anna Maria Masci, Luigi Racioppi, Enza Piccolella, and Loredana Frasca. “Hypervariable region 1 variant acting as TCR antagonist affects hepatitis C virus-specific CD4+ T cell repertoire by favoring CD95-mediated apoptosis.J Leukoc Biol 78, no. 2 (August 2005): 372–82. https://doi.org/10.1189/jlb.0804456.
Scottà C, Tuosto L, Masci AM, Racioppi L, Piccolella E, Frasca L. Hypervariable region 1 variant acting as TCR antagonist affects hepatitis C virus-specific CD4+ T cell repertoire by favoring CD95-mediated apoptosis. J Leukoc Biol. 2005 Aug;78(2):372–82.
Scottà, Cristiano, et al. “Hypervariable region 1 variant acting as TCR antagonist affects hepatitis C virus-specific CD4+ T cell repertoire by favoring CD95-mediated apoptosis.J Leukoc Biol, vol. 78, no. 2, Aug. 2005, pp. 372–82. Pubmed, doi:10.1189/jlb.0804456.
Scottà C, Tuosto L, Masci AM, Racioppi L, Piccolella E, Frasca L. Hypervariable region 1 variant acting as TCR antagonist affects hepatitis C virus-specific CD4+ T cell repertoire by favoring CD95-mediated apoptosis. J Leukoc Biol. 2005 Aug;78(2):372–382.

Published In

J Leukoc Biol

DOI

ISSN

0741-5400

Publication Date

August 2005

Volume

78

Issue

2

Start / End Page

372 / 382

Location

England

Related Subject Headings

  • fas Receptor
  • Viral Proteins
  • T-Lymphocyte Subsets
  • Serpins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Lymphocyte Activation
  • Immunology
  • Humans
  • Hepacivirus
  • Epitopes, T-Lymphocyte