PMID- 10029093
OWN - NLM
STAT- MEDLINE
DCOM- 19990304
LR  - 20111117
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 59
IP  - 4
DP  - 1999 Feb 15
TI  - Ovine MHC class II DRB1 alleles associated with resistance or susceptibility to 
      development of bovine leukemia virus-induced ovine lymphoma.
PG  - 975-81
AB  - For the further characterization of bovine leukemia virus (BLV)-induced 
      leukemogenesis, we investigated the association between polymorphism of ovine 
      leukocyte antigen (OLA)-DRB1 gene and tumor development after infection of sheep 
      with BLV. We infected 28 sheep with BLV and cloned exon 2 of the OLA-DRB1 gene 
      from asymptomatic animals and from animals with lymphoma Sequence analysis 
      revealed that, among 12 healthy sheep without any evidence of tumor, ten (83.3%) 
      carried DRB1 alleles encoding Arg-Lys (RK) at positions beta70/71 as compared 
      with only 6 (37.5%) of the 16 sheep with lymphoma, which suggested that alleles 
      encoding the RK motif might protect against development of tumors after infection 
      by BLV. By contrast, alleles encoding Ser-Arg (SR) at positions beta70/71 were 
      present at a significantly elevated frequency in sheep with lymphoma as compared 
      with the healthy carriers, which indicated that OLA-DRB1 alleles encoding the SR 
      motif might be positively related to susceptibility to tumor development. The two 
      amino acids in these motifs line a pocket that accommodates the side chain of a 
      bound peptide according to a model of the crystal structure of human leukocyte 
      antigen (HLA)-DR1. To analyze immunoreactions of sheep with alleles that encoded 
      RK or SR at beta70/71, we selected sheep with either the RK/SR genotypes or the 
      SR/SR genotypes and immunized them with a mixture of multiple synthetic antigenic 
      peptides that corresponded to T-helper, T-cytotoxic, and B-cell epitopes of the 
      BLV envelope glycoprotein gp51. Two weeks after the last immunization, all of the 
      sheep were challenged with BLV. Sheep with the RK/SR genotype produced 
      neutralizing antibodies against BLV; they eliminated BLV completely within 28 
      weeks of the BLV challenge, and they gave strong lymphocyte-proliferative 
      responses to the peptides used for immunization. Moreover, such animals did not 
      develop lymphoma. By contrast, sheep with the SR/SR genotype continued to produce 
      BLV throughout the experimental period and developed terminal disease. Our 
      results indicate that the differences in immunoresponse were due to differences 
      in major histocompatibility complex class II alleles and reflected the risk of 
      BLV-induced leukemogenesis. In addition, it appears that susceptibility to tumor 
      development may be determined to some extent by polymorphic residues binding to 
      antigenic peptides directly within the binding cleft of the OLA-DR molecule.
FAU - Nagaoka, Y
AU  - Nagaoka Y
AD  - Tsukuba Life Science Center, The Institute of Physical and Chemical Research 
      (RIKEN), Ibaraki, Japan.
FAU - Kabeya, H
AU  - Kabeya H
FAU - Onuma, M
AU  - Onuma M
FAU - Kasai, N
AU  - Kasai N
FAU - Okada, K
AU  - Okada K
FAU - Aida, Y
AU  - Aida Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - *Alleles
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cattle
MH  - Disease Susceptibility
MH  - Enzootic Bovine Leukosis/*immunology
MH  - Genotype
MH  - HLA-DR Antigens/*genetics
MH  - HLA-DRB1 Chains
MH  - Immunization
MH  - Leukemia Virus, Bovine/immunology
MH  - Lymphoma/*immunology
MH  - Molecular Sequence Data
MH  - Sheep
EDAT- 1999/02/24 00:00
MHDA- 1999/02/24 00:01
CRDT- 1999/02/24 00:00
PHST- 1999/02/24 00:00 [pubmed]
PHST- 1999/02/24 00:01 [medline]
PHST- 1999/02/24 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1999 Feb 15;59(4):975-81.