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Function and disease susceptibility of bovine MHC class II molecule

Research Project

Project/Area Number 09660334
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Basic veterinary science/Basic zootechnical science
Research InstitutionThe Institute of Physical and Chemical Research (RIKEN)

Principal Investigator

AIDA Yoko  RIKEN,Molecular cell Science Laboratory, Scientist, 分子細胞生物学研究室, 先任研究員 (50182994)

Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1998: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsMHC / class II gene / bovine leukocyte antigen / BoLA-DRB3 / polymorphism / resistant allele / bovine leukemia virus / lymphoma
Research Abstract

To investigate the relationship between polymorphism of bovine lymphocyte antigen (BoLA) gene and resistance or susceptibility to BLV-induced lymphoma, exon 2 of the BoLA-DRB3 gene which is highly polymorphic was cloned from 54 BLV-infected animals with 3 independent stages such as an aleukemic healthy, persistent lymphocytosis and lymphoma, and the nucleotide sequences were determined. Sequence analysis revealed that the BoLA-DRB3 alleles encoding Val at position 78 may be associated with resistance to BLV-induced lymphoma. Alleles encoding Val at position 78 were characterized by Arg or Lys, which represent a positive charge at position 71 and by Glu, which represents a negative charge at position 74. By contrast, alleles encoding Tyr at position 78, have amino acids such as Ala, Asn or Tyr, which represent a neutral charge at position 74 and were associated with susceptibility to lymphoma.
Next, to confirm the association between polymorphism of MHC class II gene and leukemia, we infected 28 sheep with BLV.Among the 16 sheep with lymphoma, 38% carry specific alleles of the ovine leukocyte antigen (OLA)-DRB1 Arg^<70>-Lys^<71> (RK) as compared to 83% among the 12 BLV-infected sheep at the asymptomatic stage. To analyze the immunoreaction of sheep with allele of OLA-DRB1 RK, we immunized sheep carrying either a RK/X genotype or a X/X genotype with a mixture of synthetic multiple antigenic peptides of T-helper, T-cytotoxic, and B-cell epitopes of BLV envelope glycoprotein gp 51, and two weeks after the last immunization, all sheep were challenged with blood from a BLV-infected sheep. Sheep carrying resistant allele showed high immunoresponse against the mixed peptides and did not proceeded to ieukemia. Our results indicate that difference of immunoresponse resulted due to difference of MHC class II alleles and involved the risk of BLV-induced leukemogenesis.

Report

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

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Nagaoka, Y.,et al.: "Ovine MHC class II DRBl alleles associated with resistance or susceptibility to development of bovine leukemia virus-induced ovine lymphoma." Cancer Res.,. in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Inabe K.,et al.: "The YXXL sequences of bovineleukemia virus transmembraneprotein are required formaintenance of viral penetration andincorporation of viral envelopeprotein into virion." J.Virology. 73. 1293-1301 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 間 陽子: "疾患感受性を規定するウシMHCクラスII分子の構造と機能" 動物遺伝研究会誌. 26. 1-12 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tajima S.,et al.: "Complete bovine leukemia virus (BLV) provirus is conserved in BLV-infected cattle throughout the course of B-cell lymphosarcoma." J.Virology. 243. 235-246 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Inabe K.,et al.: "Transmission and propagation in cell culture of virus produced by cell transfected with an infectious molecular clone of bovine leukemia virus." Virology. 245. 53-64 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tajima S.,et al.: "Function and conformation of wild-type p53 protein are influenced by mutations in bovine leukemia virus-induced B-cell lymphosarcoma." Virology. 243. 235-246 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tani K., Asahina M., Wu D.L., Ajito T., Murakami K., Goryo M., Aida Y., Davis W.C., Okada K.: "Further analysis of the phenotype and distribution of tumor cells in sporadic B-cell and T-cell lymphomas in the lymph node and spleen of cattle." Vet.Immunol.Immunopathol.55. 283-290 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Aida Y., Nishino Y., Amanuma H., Murakami K., Okada K.and Ikawa Y.: "The role of tumor-associated antigen in bovine leukemia virus-induced lymphosarcoma." Leukemia. 11. S216-218 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Zhuang, W., Tajima S., Okada K., Ikawa Y.and Aida Y.: "Point mutation of p53 tumor suppressor gene in bovine leukemia virus-induced lymphosarcoma." Leukemia. 11. S344-346 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Koguchi A., Goryo M., Aida Y.and Okada K.: "Tumor-associated antigen in lymph nodes during the progression of enzootic bovine leukosis." Leukemia. 11. S221-222 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tajima S., Zhuang, W., Kato MV., Okada K., Ikawa Y.and Aida Y.: "Function and conformation of wild-type p53 protein are influenced by mutations in bovine leukemia virus-induced B-cell lymphosarcoma." Virology. 243. 235-246 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Inabe K., Ikuta K.and Aida Y.: "Transmission and propagation in cell culture of virus produced by cell transfected with an infectious molecular clone of bovine leukemia virus." Virology. 245. 53-64 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tajima S., Ikawa Y.and Aida Y.: "Complete bovine leukemia virus (BLV) provirus is conserved in BLV-infected cattle throughout the course of B-cell lymphosarcoma." J.Virology. 243. 235-246 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tana, Watarai S., Onuma M., Aida Y., Kakidani H., Kodama H., and Yasuda T.: "Antitumor effect of diphtheria toxin A-chain gene containing cationic liposomes conjugated with monoclonal antibody directed to tumor-associated antigen of bovine leukemia cells." Jpn.J.Cancer Res.84. 1202-1211 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Inabe K., Nishizawa M.and Aida Y.: "The YXXL sequences of bovine leukemia virus transmembrane protein are required for maintenance of viral penetration and incorporation of viral envelope protein into virion." J.Virology.73. 1293-1301 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagaoka, Y., Kabeya H., Onuma M., Kasai N., Okada K.and Aida Y.: "Ovine MHC class II DRB1 alleles associated with resistance or susceptibility to development of bovine leukemia virus-induced ovine lymphoma." Cancer Res.59. (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 間 陽子: "疾患感受性を規定するウシMHCクラスII分子の構造と機能" 動物遺伝研究会誌. 26. 1-12 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nagaoka, Y., et al.: "Ovine MHC class II DRB1 alleles associated with resistance or susceptibility to development of bovine leukemia virus-induced ovine lymphoma." Cancer Res.(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 間 陽子、長岡淑子: "ウシMHC遺伝子" 日本組織適合性学会誌. 3. 213-225 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 間 陽子: "牛白血病ウイルスによる白血病発症とMHC" 獣医臨床遺伝研究会誌. 5-6. 14-17 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 間 陽子: "疾患感受性を規定するウシMHCクラスII分子の構造と機能" 動物遺伝研究会誌. (印刷中). (1998)

    • Related Report
      1997 Annual Research Report

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

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