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

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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.