| Co-Investigator(Kenkyū-buntansha) |
MORITA Mitsuo Livestock Improvement Association of Japan Maebashi institute of animal science Dibision of genetics Blood typing laboratory, Head, 家畜改良技術研究所・遺伝検査部, 課長
MORITA Hiroshi Chisso Corporation Yokohama Research Center, Bench researcher, 横浜研究所, 主任研究員
TAJIMA Shigeru RIKEN Molecular Cell Science Laboratory, Special post doctoral fellow, 分子細胞生物学研究室, 基礎科学特別研究員 (60311346)
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| Budget Amount *help |
¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2000: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 1999: ¥8,300,000 (Direct Cost: ¥8,300,000)
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| Research Abstract |
Bovine leukemia virus (BLV)is associated with enzootic bovine leukosis and is closely related to human T-cell leukemia virus types 1. We investigated the relationship between polymorphism of bovine MHC(BoLA)gene and resistance or susceptibility to BLV-induced lymphoma. The nucleotide sequencing of exon 2 of the BoLA-DRB3 gene, which is highly polymorphic, of 81 BLV-infected animals with 3 independent stages such as an aleukemic healthy, persistent lymphocytosis and lymphoma was determined by PCR-Sequenced-Based Typing method. Sequence analysis revealed that alleles eccoding Arg or Lys, Glu, Arg and Val at residues 71, 74, 77 and 78 of beta chain of DR might be related with resistance to tumor development. By contrast, 70% of cattle with lymphoma were homozygous for alleles encoding Ala, Thr and Tyr at residues 74, 77 and 78. Next, to confirm the association between polymorphism of MHC class II gene and lymphoma, we infected 28 sheep with BLV.Among the 16 sheep with lymphoma, 38% carried specific alleles of the ovine MHC(OLA)-DRBI gene encoding Arglays(RK)at residues 70 and 71 as compared to 83% among the 12 sheep at the asymptomatic stage. Futhermore, we immunized sheep carrying either a RK/XX genotype or a XX/XX genotype with a synthetic antigenic peptides of T-helper, T-cytotoxic, and B-cell epitopes of BLV envelope glycoprotein gp51, and two weeks after the last immunization, all sheep were challenged with blood from a BLV-inftected sheep. Sheep carrying resistant allele showed high immunoresponse against the mixed peptides and did not proceeded to leukemia.
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