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Immunohematologic studies on the SDF-1/CXCR-4 system with monoclonal antibod.

Research Project

Project/Area Number 09671107
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

HORI Toshiyuki  Kyoto University, Institute for Virus Research Instructor, ウイルス研究所, 助手 (70243102)

Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsCXCR-4 / CDF-1 / chemokine / HIV-1 / CXCR4 / モノクローナル抗体 / HIV
Research Abstract

Three mAbs, termed IVR7, AI58, and THS123, were generated and demonstrated to react specifically with human CXCR-4-transfected COS-7 cells. THSl23 could immunoprecipitate a component with an apparent mol wt of 47 kD from CXCR-4^+ cells. Flow cytometric analysis showed that most of the hematopoietic cell lines and some non-hematopoietic cell lines expressed CXCR-4. A fraction of normal peripheral blood mononulcear cells expressed CXCR-4 but neutrophils were negative. Two color analysis revealed that the majority of but not all T cells, virtually all B cells and all moncytes expressed CXCR-4 while it was hardly detectable on NK cells. As to differentiated helper T cells, Th2 but not Th1 expressed CXCR-4. It was also found that IL-4 could induce expression of functional CXCR-4 on Th1. Thus, expression of CXCR-4 is not ubiquitous but rather cell type-specific in hematopoietic cells.
Entry of HIV-1 is initiated by interaction of the envelope protein gp120 with CD4 and one of the relevant chemokine receptors. Although the V3 region of gp120 is speculated to be involved in interaction with chemokine receptors, it is still unclear if the V3 region can directly bind to them. Using synthetic V3 peptides that correspond to the V3 regions of gp120 of T-tropic, M-tropic and dual tropic HIV-1, we could demonstrate that V3 peptides of T-tropic and dual tropic strains but not that of an M-tropic strain could directly bind to CXCR-4, which indicate that the V3 region of gp120 can bind to the relevant chemokine receptor by itself without CD4 or other domains of gp120.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Toshiyuki Hori: "Delineation of CXCR-4 as an entry cofactor for T-tropie HIV-1 by monoclonal antibedies" Immunology Letters. 56. 15-15 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Toshiyuki Hori: "Detection and delineation of CXCR-4(fusin) as an entry and fasion cofactor for T-tropic HIV-1 by three difterent monoclonal antibodies" The Journal of Immunology. 160. 180-188 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masaaki Arai: "Human T-cell leukemia virus type I Tax protein induces the expression of lymphocyte chemoattracfant SDF-1/PBSF" Virology. 241. 298-303 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Huiling Hu: "Imternalization of CXCR-4 is not required for its coreceptor activity for HIV-1 entry" Archives of Virology. 143. 851-861 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Patrick Jourdan: "Interleukin-4 induces functional expression of CXCR-4 on human Th1 and Th2 cells which resuHs in activation of ERK-2 MAP Kinase" The Journal of Immunology. 160. 4153-4157 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hitoshi Sakaida: "T-tropic human immunodeficiency virus type 1(HIV-1)-derived V3 loop peptide directly bind to CXCR-4 and inhibit T-tropic HIV-1 intection" The Journal of Virology. 72. 9763-9770 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Toshiyuki Hori, Hitoshi Sakaida, Akihiko Sato, Toshihiro Nakajima, Hisatoshi Shida, Osamau Yoshie, and Takashi Uchiyama.: "Delineation of CXCR-4 as an entry cofactor for T-tropic HIV-1 by monoclonal antibodies." Immunolgy Letters. 56. 15 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Toshiyuki Hori, Hitoshi Sakaida, Akihiko Sato, Toshihiro Nakajima, Hisatoshi Shida, Osamu Yoshie, and Takashi Uchiyama.: "Detection and delineation of CXCR-4 (fusin) as an entry and fusion cofactor for T-tropic HIV-1 by three different monoclonal antibodies." The Journal of Immunology. 160. 180-188 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masaaki Arai, Takashi Ohhashi, Tomonori Tsukahara, Toshiyuki Hori, Takashi Uchiyama, Naoki Yamamoto, Mari Kannagi, and Masahiro Fujii.: "Human T-cell leukemia virus type 1 Tax protein induces the expression of lymphocyte chemoattractant SDF-1/PBSF" Virology. 241. 298-303 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Huiling Hu, Tatsuo Shioda, Toshiyuki Hori, Chiakaya Moriya, Atsushi Kato, Yuko Sakai, Kouji Matsushima, Takashi Uchiyama, and Yoshiyuki Nagai.: "Internalization of CXCR-4 is not required for its coreceptor activity for HIV-1 entry." Archives of Virology. 143. 851-861 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Patrick Jourdan, Claire Abbal, Nelly Noraz, Toshiyuki Hori, Takashi Uchiyama, Jean Bousquet, Naomi Taylor, Jerome Pene, and Hans Yssel.: "Interleukin-4 induces functional expression of CXCR-4 on human Th1 and Th2 cells which results in activation of ERK-2 MAP kinase following stimulation of CXCR-4-expressing T cells with SDF-1." The Journal of Immunology. 160. 4153-4157 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hitoshi Sakaida, Toshiyuki Hori, Akihito Yonezawa, Akihiko Sato, Yoshitaka Isaka, Osamu Yoshie, Toshio Hattori, and Takashi Uchiyama.: "T-tropic human immunodeficiency virus type 1 (HIV-1)-derived V3 loop peptides directly bind to CXCR-4 and inhibit T-tropic HIV-1 infection." The Journal of Virology. 72. 9763-9770 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Toshiyuki Hori: "Delineation of CXCR-4 as an entry cofactor for T-tropic HIV-1 by monclonal antibodies" Immunology Letters. 56. 15-15 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Toshiyuki Hori: "Detection and delineation of CXCR-4(fusin)as an entry and fusin cotactor for T-trepic HIV-1 by three ditterent monoclonal antibodies" The Journal of Immunology. 160. 180-188 (1988)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masaaki Arai: "Human T cell leukemia virus type 1 Tax protein induces the expression of lymphocyte chemoattractant SDF-1/PBSF" Virology. 241. 298-303 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Huiling Hu: "Internalization of CXCR-4 is not required for its corecepter activity for HIV-1 entry" Archives of Virology. 143. 851-861 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Patrick Jourdan: "Interleukin-4 induces functional expression of CXCR-4 on human Th1 and Th2 cells which results in activation of ERK-2 MAP kinase" The Journal of Immunology. 160. 4153-4157 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hitoshi Sakaida: "T-tropic human immunodeficiency virus type 1(HIV-1)-derived V3 loop peptides derectly bind to CXCR-4 and inhibit T-fropic Hiv-1 intecting" The Journal of Virology. 72. 9763-9770 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Hori: "Delineation of CXCR-4 as an entry cofactor for T-tropic HIV-1 by monoclonal anfibodies" Immunology Letters. 56. 15-15 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.Hori: "Detection and delineation of CXCR-4(fnsin)as an enfry and fasim Cofactor for T-tropic HIV-1 by three different monoclonal anfibodies" The Journal of Immunology. 160. 180-188 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Arai: "Human T-cell leukemia virus type I Tax protein induces the expression of lymphocyte chemo atlracf ant SDF-1/PBSF" Virofogy. (発表予定).

    • Related Report
      1997 Annual Research Report
  • [Publications] H.Hu: "Internalization of CXCR-4 is not required for its coreceptor activity for HIV-1 entry" Archives of Virology. (発表予定).

    • Related Report
      1997 Annual Research Report
  • [Publications] P.Jourdan: "Inferleukin-4 indnces functional expression of CXCR-4 on human Th1 and Th2 cells which results in activation of ERK-2 MAP kinuse" The Journal of Immunology. (発表予定).

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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