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Detection of cattle associated with resistance or susceptibility to bovine leukemia virus-induced kymphoma by analysis of polymorphism of the bovine MHC genes

通过牛 MHC 基因多态性分析检测牛对牛白血病病毒诱发的鸡肿瘤的抵抗或易感性

基本信息

批准号：
11556061
负责人：
AIDA Yoko
金额：
$ 8.7万
依托单位：
RIKEN
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

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.

牛白血病病毒（BLV）与地方性牛白血病有关，与人类T细胞白血病病毒1型密切相关。研究了牛MHC（BoLA）基因多态性与BLV诱导的淋巴瘤的易感性和抗性的关系。采用PCR-测序分型法对81只BLV感染动物的BoLA-DRB 3基因外显子2进行了核苷酸序列测定。序列分析表明，DR β链第71、74、77和78位残基上编码Arg或Lys、Glu、Arg和瓦尔的等位基因可能与DR抗肿瘤有关。相比之下，70%患有淋巴瘤的牛在残基74、77和78处编码Ala、Thr和Tyr的等位基因是纯合的。其次，为了证实MHC Ⅱ类基因多态性与淋巴瘤之间的关联，我们用BLV感染了28只绵羊。在16只淋巴瘤绵羊中，38%的绵羊携带编码Arglays（RK）的绵羊MHC（奥拉）-DRBI基因的第70和71位残基的特异性等位基因，而在12只无症状的绵羊中，这一比例为83%。随后，我们用BLV包膜糖蛋白gp 51的T辅助细胞、T细胞毒性细胞和B细胞表位的合成抗原肽免疫携带RK/XX基因型或XX/XX基因型的绵羊，并在最后一次免疫后两周，用来自BLV感染绵羊的血液攻击所有绵羊。携带抗性等位基因的绵羊对混合肽表现出高的免疫应答，并且没有发生白血病。