Antibodies against B7-DC with differential binding properties exert opposite effects.
Programmed cell death 1 (PD-1) is an immunoregulatory receptor on T cells that binds two ligands, B7-H1 and B7-DC. Although accumulating reports suggest a critical role for the B7-H1:PD-1 pathway in peripheral tolerance, the actual involvement of B7-DC has not been well confirmed. Here, we established a new MAb against mouse B7-DC (MIH37) and compared its functional properties with a previously established anti-B7-DC MAb (TY25). Binding analyses using flow cytometry demonstrated that MIH37 showed an approximately four-fold higher binding affinity to B7-DC and stronger inhibitory effects on B7-DC:PD-1 binding. In contrast to the effects of TY25, treatment with MIH37 at both sensitization and challenge inhibited hapten-induced contact hypersensitivity reactions. Furthermore, the addition of MIH37 inhibited OVA-specific T cell responses in vitro. The inhibitory effects of MIH37 were counteracted by co-blockade with PD-1 and absent in PD-1-deficient mice, suggesting PD-1-dependent action of MIH37. Our present results suggest that greater complexities of PD-1-mediated functions are induced via ligand binding for controlling immunity and tolerance.
Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Patcharee
P
Ritprajak
Masaaki
M
Hashiguchi
Hisaya
H
Akiba
Hideo
H
Yagita
Ko
K
Okumura
Miyuki
M
Azuma
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000276:immunology* / Q000627:therapeutic use; D000918:Antibody Specificity / Q000276:immunology*; D060890:B7-H1 Antigen / Q000276:immunology / Q000378:metabolism; D003877:Dermatitis, Contact / Q000628:therapy; D005434:Flow Cytometry; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D061166:Peripheral Tolerance / Q000276:immunology*; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding
D000911:Antibodies, Monoclonal; D060890:B7-H1 Antigen; C556978:Pdcd1lg2 protein, mouse; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor