Structure, function and disease susceptibility of bovine MHC class II molecules

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The bovine leukocyte antigen (BoLA)class II genes code for highly polymorphic transmembrane glycoproteins that present antigenic peptides to helper T cells. The BoLA-DRB3 is thought to be the most functionally significant as it is actively transcribed and in excess of 102 alleles have been characterized for this locus. First, we developed the technique of polymerase chain reaction-sequence based typing(PCR-SBT)which can assign DRB3 alleles in DNA sequence level and would allow fast screening of large numbers of animals. Next, we designed to determine the nucleotide sequences of exon 2 of BoLA-DRB3 alleles in a total of 419 animalks from four distinct cattle breeds such as Japanese Black. Japanese Shorthorn Holstein and Jersey by our PCR-SBT method, and the allele frequencies and the phylogenetic relationship of BoLA-DRB3 alleles and the genetic background of these populations are discussed.The nucleotide sequencing of exon 2 of the BoLA-DRB3 gene, which is highly polymorphic, of 81 bov … More ine leukemia virus(BLV)-infected animals with 3 independent stages such as an aleukemic healthy, persistent lymphocytosis(PL)and lymphoma was determined by PCR-sequenced-based typing. We identified 23 distinct BoLA-DR83 alleles, including 3 new alleles. The population of healthy cattle positive for BoLA-DRB3^*14011 was higher than the proportion-bearing individuals in 200 control cases that were positive for the same allele. By contrast, the BoLA-DRB3^*1601 alleles was found most frequently in cattle with PL and lymphoma. Sequence analysis revealed that, approximately 56 % of 43 BLV-infected but healthy cattle carry at least one BoLA-DRB3 allele encoding Arg^<71> of Lys^<71>, Glu^<74>, Arg^<77> and Val^<78> of β1 domain of DR molecule, which suggested that alleles encoding the KERV and RERV motifs might protect against tumor development. By contrast, approximately 70% of 23 BLV-infected cattle with lymphoma carry two alleles encoding Ala^<74>, Thr^<77> and Tyr^<78>, indicating that the ATY/ATY genotype might be associated with susceptibility to lymphoma. Such, these results suggest that the existence of alleles associated with resistance and susceptibility to BLV-induced leukemogenesis.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)-DRB1 gene encoding Arg-Lys(RK)at residues 70 and 71 as compared to 83% among the 12 sheep at the asymptomatic stage. Furthermore, 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 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 leukemia. Less