Identification and characterization of bovine programmed death-ligand 2.
Previous reports from this group have indicated that the immunoinhibitory programmed death (PD)-1 receptor and its ligand, PD-L1, are involved in the mechanism of immune evasion of bovine chronic infection. However, no functional analysis of bovine PD-L2 in cattle has been reported. Thus, in this study, the molecular function of bovine PD-L2 was analyzed in vitro. Recombinant PD-L2 (PD-L2-Ig), which comprises an extracellular domain of bovine PD-L2 fused to the Fc portion of rabbit IgG1, was prepared based on the cloned cDNA sequence for bovine PD-L2. Bovine PD-L2-Ig bound to bovine PD-1-expressing cells and addition of soluble bovine PD-1-Ig clearly inhibited the binding of PD-L2-Ig to membrane PD-1 in a dose-dependent manner. Cell proliferation and IFN-γ production were significantly enhanced in the presence of PD-L2-Ig in peripheral blood mononuclear cells (PBMCs) from cattle. Moreover, PD-L2-Ig significantly enhanced IFN-γ production from virus envelope peptides-stimulated PBMCs derived from bovine leukemia virus-infected cattle. Interestingly, PD-L2-Ig-induced IFN-γ production was further enhanced by treatment with anti-bovine PD-1 antibody. These data suggest potential applications of bovine PD-L2-Ig as a therapy for bovine diseases.
Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818.
Asami
A
Nishimori
Satoru
S
Konnai
Ryoyo
R
Ikebuchi
Tomohiro
T
Okagawa
Chie
C
Nakajima
Yasuhiko
Y
Suzuki
Claro N
CN
Mingala
Shiro
S
Murata
Kazuhiko
K
Ohashi
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001483:Base Sequence; D002417:Cattle; D003001:Cloning, Molecular; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D010802:Phylogeny; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D011485:Protein Binding; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D007371:Interferon-gamma
bovine leukemia virus; gamma-interferon; programmed death-1; programmed death-ligand 2