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Effects of HLA-antigen presentation machinery on the antiviral effectiveness of T lymphocytes.

Research Project

Project/Area Number 17590419
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionKumamoto University

Principal Investigator

UENO Takamasa  Kumamoto University, Center for AIDS Research, Lecturer, エイズ学研究センター, 講師 (10322314)

Co-Investigator(Kenkyū-buntansha) TAKIGUCHI Masafumi  Kumamoto University, Center for AIDS Research, Professor, エイズ学研究センター, 教授 (00183450)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,600,000 (Direct Cost: ¥2,600,000)
KeywordsAntigen / T lymphocyte / T cell receptor / HIV / AID S / antiviral activity / MHCクラスI / 細胞傷害性T細胞 / 抗原提示 / 抗体 / ファージディスプレイ
Research Abstract

A less effective HIV-specific cytotoxic T lymphocyte (CTL) response during a chronic HIV infection is an important factor for progressive immunopathogenesis, but how such CTLs are generated and accumulated remains elusive. Herein, we characterized CTL responses toward Pol, Env, and Nef optimal epitopes presented by HLA-B^*35, a human leukocyte antigen (HLA) associated with rapid disease progression. We found CTL escape variants within Pol and Nef epitopes that affected recognition by T cell receptors, although there was no mutation within the Env epitope. Analysis of peptide-HLA tetrameric complexes revealed that CD8 T cells exclusively specific for the Nef variant were generated following domination by the variant viruses. The variant-specific cells were capable of secreting antiviral cytokines but showed impaired antigen-specific proliferative responses ex vivo, whereas wild-type-specific ones had potent activities. Moreover, clonotypic CD8 T cells specific for the Pol variant showed diminished proliferation, whereas Env-specific ones had no functional he terogeneity. Taken together, our data indicate that antigenic variations that lead to a loss of T cell receptor recognition result not solely in the escape from established CTL responses, but also in decoy antigens that recruit less effective HlV-specific CTLs. Such a decoy antigen could have in part an actively negative effect on antiviral immune responses during a chronic HIV infection, providing us insights into the progressive immunopathogenesis as well as vaccine design against HIV infections.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (8 results)

All 2007 2006 2005

All Journal Article (8 results)

  • [Journal Article] Altering effects of antigenic variations of HIV-1 on the antiviral effectiveness of HIV-specific CTLs2007

    • Author(s)
      Takamasa Ueno, et al.
    • Journal Title

      The Journal of Immunology 178

      Pages: 5513-5523

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Altering effects of antigenic variations in HIV-1 on antiviral effectiveness of HIV-specific CTLs2007

    • Author(s)
      Takamasa Ueno, et al.
    • Journal Title

      The Journal of Immunology 178

      Pages: 5513-5523

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Altering effects of antigenic variations in HIV-1 on antiviral effectiveness of HIV-specific CTLs.2007

    • Author(s)
      Takamasa Ueno, et al.
    • Journal Title

      Journal of Immunology (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] HLAアリル多型性とHIV感染症2006

    • Author(s)
      上野貴将
    • Journal Title

      診断と治療 94(12)

      Pages: 121-124

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] HIVに対する細胞傷害性T細胞の免疫応答2005

    • Author(s)
      上野貴将ら
    • Journal Title

      The Journal of AIDS Research 7(3)

      Pages: 155-160

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cytotoxic T lymphocyte-mediated immune responses to HIV.2005

    • Author(s)
      Takamasa Ueno, et al.
    • Journal Title

      The Journal of AIDS Research 7(3)

      Pages: 155-160

    • NAID

      130003710521

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cytotoxic T lymphocyte-mediated immune responses to HIV.2005

    • Author(s)
      Takamasa Ueno, Masafumi Takiguchi
    • Journal Title

      The Journal of AIDS Research 7・3

      Pages: 155-160

    • NAID

      130003710521

    • Related Report
      2005 Annual Research Report
  • [Journal Article] クラスI MHC拘束性抗原提示機構2005

    • Author(s)
      上野貴将
    • Journal Title

      臨床免疫学(上) 63・4

      Pages: 304-308

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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