title: Molecular cloning of bovine lymphocyte activation gene-3 and its expression characteristics in bovine leukemia virus-infected cattle.
abstract: Lymphocyte activation gene-3 (LAG-3), a major histocompatibility complex (MHC) class II binding CD4 homologue has recently been shown as one of the mechanisms for down-regulating immune responses during chronic disease progression. For the first time, we cloned LAG-3 from two breeds of cattle (Holstein and Japanese Black), and analyzed its expression levels in cattle infected with bovine leukemia virus (BLV), a chronic viral infection that leads to immuno-suppression. The cloned cDNA of bovine LAG-3 have an open reading frame of 1551 nucleotides, encoding a polypeptide of 515 amino acids in length. Similar to the swine LAG-3, the bovine LAG-3 protein sequence consisted of four extracellular domains, a transmembrane domain and an inhibitory motif, KTGELE. We found that the bovine LAG-3 mRNA transcripts were expressed predominantly on T-cells such as CD4(+) and CD8(+) cells, among peripheral blood mononuclear cells. In subsequent expression analysis, LAG-3 mRNA expression on CD4(+) T-cells from BLV-infected cattle was upregulated compared to that in normal cattle. Comparable results were obtained with CD8(+) T-cells from cattle infected with BLV. We further observed strong upregualtion of MHC class II molecule, the ligand for LAG-3 in BLV-infected cattle. These findings indicate an important role for inhibitory receptor molecules such as LAG-3 in chronic bovine infections and future studies will elucidate the specific role of LAG-3 in bovine diseases.
authors: Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors: Tatsuya
authors: T
authors: Shirai
authors: Satoru
authors: S
authors: Konnai
authors: Ryoyo
authors: R
authors: Ikebuchi
authors: Tomohiro
authors: T
authors: Okagawa
authors: Saori
authors: S
authors: Suzuki
authors: Yuji
authors: Y
authors: Sunden
authors: Misao
authors: M
authors: Onuma
authors: Shiro
authors: S
authors: Murata
authors: Kazuhiko
authors: K
authors: Ohashi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000502:physiology; D001483:Base Sequence; D002417:Cattle; D003001:Cloning, Molecular; D016583:Enzootic Bovine Leukosis / Q000235:genetics / Q000276:immunology*; D020869:Gene Expression Profiling / Q000662:veterinary; D001909:Leukemia Virus, Bovine / Q000276:immunology*; D008969:Molecular Sequence Data; D010802:Phylogeny; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D020539:Sequence Analysis, Protein / Q000662:veterinary; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; D000093322:Lymphocyte Activation Gene 3 Protein