The Influence of Ovine MHC Class IIDRB1Alleles on Immune Response in Bovine Leukemia Virus Infection

Abstract

We have reported previously that the alleles of the ovine leukocyte antigen (OLA)‐DRB1 gene that encode the Arg‐Lys (RK) motif and the Ser‐Arg (SR) motif at positions β70/71 of the OLA‐DRβ1 domain are associated with resistance and susceptibility, respectively, to development of bovine leukemia virus (BLV)‐induced ovine lymphoma. Here, to investigate the different immune response in sheep that carried alleles associated with resistance and susceptible for 30 weeks after infection with BLV, we selected sheep that had the RK/RK or SR/SR genotype among the 52 sheep analyzed by polymerase chain reaction‐restriction fragment length polymorphism and DNA sequencing of PCR product for the OLA‐DRB1 exon 2 and infected them with BLV. Although the number of BLV‐infected cells and virus titer had been maintaining low levels throughout the experimental period, the sheep with the RK/RK genotype could induce expansion of CD5− B‐cells and rapid production of neutralizing antibody in the early phase of infection. The level of incorporation of [3H]thymidine by peripheral blood mononuclear cells from the sheep with RK/RK genotype gave a strong response to BLV virion antigen and synthetic antigenic peptides that corresponded to T‐helper epitope of the BLV envelope glycoprotein gp51. In contrast, the sheep with SR/SR genotype showed a strong response to BLV virion antigen and synthetic antigenic peptides that corresponded to T‐cytotoxic and B‐cell epitopes. In such cases, the animals with the RK/RK strongly expressed IFN‐7, the animals with SR/SR genotype strongly expressed IL‐2. To determine the proliferating cells, we tried a blocking assay with monoclonal antibodies such as anti‐CD4, ‐CD8 and ‐DR molecule. We found that these proliferating cells were MHC‐restricted CD4+ T‐cells.

Allelic Diversity of Major Histocompatibility Complex Class II DRB Gene in Indian Cattle and Buffalo

“…DRB3 ( BoLA-DRB3 ) has been found to be highly polymorphic and is responsible for the differences in the susceptibility to infectious disease. DRB1 is a pseudogene and DRB2 gene is transcribed at very low levels in lymphocyte tissue [9, 10]. Polymorphism of BoLA-DRB3 is confined mainly to second exon that encodes for β 1 domain, responsible for peptide-binding sites.…”

Tumor necrosis factor-alpha genetic polymorphism may contribute to progression of bovine leukemia virus-infection

“…In genetic analysis of BLV-infection, previous studies revealed the polymorphism in bovine leukocyte antigen (BoLA)-DRβ chain associated with resistance to expansion of BLV [27] and PL [28]. Furthermore, it appeared that ovine leukocyte antigen (Ovar)-DRB1 alleles encoding the RK motif at positions 70-71 of the Ovar-DRβ chain might protect against tumor development after experimental infection of sheep with BLV [29], and sheep with alleles encoding the RK motif could induce cellular immunity [30]. In this report, we showed that polymorphisms in the TNF-α promoter, -824G, which indicated low transcriptional activity, is associated with the BLV-induced lymphoma and elevation of provirus load in BLV-infected individuals.…”

OLA-DRB1 microsatellite variants are associated with ovine growth and reproduction traits

“…Such associations could be due to differences in disease resistance between carriers of various MHC haplotypes that can in turn affect the individual growth performance. In sheep, associations of DRB1 alleles with resistance to bovine leukaemia virus infection [16] or parasitic nematodes [26] are known. We found the birth weight of lambs to be significantly associated with DRB1 microsatellite alleles (Tab.…”