Function and disease susceptibility of bovine MHC class II molecule

牛MHC II类分子的功能和疾病易感性

基本信息

批准号：
09660334
负责人：
AIDA Yoko
金额：
$ 2.43万
依托单位：
The Institute of Physical and Chemical Research (RIKEN)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09660334/
关键词：
MHC class II gene bovine leukocyte antigen BoLA-DRB3 polymorphism resistant allele bovine leukemia virus lymphoma

项目摘要

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.

研究牛淋巴细胞抗原（BOLA）基因的多态性与BLV诱导的淋巴瘤的耐药性或易感性，Bola-DRB3基因的外显子2，这是高度多态性的，从54个BLV感染的动物中克隆了54个BLV感染的动物。确定核苷酸序列。序列分析表明，在78位置编码Val的Bola-DRB3等位基因可能与对BLV诱导的淋巴瘤的抗性有关。编码Val在78处编码Val的等位基因的特征是ARG或LYS，代表位置71和GLU的正电荷，GLU代表位置74处的负电荷。相比之下，编码Tyr在78位置的等位基因，具有ALA，ASN或TYR等氨基酸的等位基因，如74的位置和MISSISS II均与lymphibility succents ii nepribistion.Minsive.Snextibles.s nemply.s相关性。 Gene和Leukemia，我们用Blv.Among感染了28只绵羊，其中16只绵羊带有淋巴瘤，其中38％带有卵子白细胞抗原（OLA）-DRB1 arg^<70> -lys^<71>（RK）的特定等位基因，而在12 blv又是在AS-AS-AS-ASPENS-PENCEMPTAMES中的83％。 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受到BLV感染的绵羊的血液的挑战。携带抗药性等位基因的绵羊对混合肽表现出很高的免疫响应，并且没有进入Ieukemia。我们的结果表明，由于MHC II类等位基因的差异，导致免疫激素的差异，并涉及BLV诱导的白血病的风险。