title: B7-h2 is a costimulatory ligand for CD28 in human.
abstract: CD28 and CTLA-4 are cell surface cosignaling molecules essential for the control of T cell activation upon the engagement of their ligands B7-1 and B7-2 from antigen-presenting cells. By employing a receptor array assay, we have demonstrated that B7-H2, best known as the ligand of inducible costimulator, was a ligand for CD28 and CTLA-4 in human, whereas these interactions were not conserved in mouse. B7-H2 and B7-1 or B7-2 interacted with CD28 through distinctive domains. B7-H2-CD28 interaction was essential for the costimulation of human T cells' primary responses to allogeneic antigens and memory recall responses. Similar to B7-1 and B7-2, B7-H2 costimulation via CD28 induced survival factor Bcl-xL, downregulated cell cycle inhibitor p27(kip1), and triggered signaling cascade of ERK and AKT kinase-dependent pathways. Our findings warrant re-evaluation of CD28 and CTLA-4's functions previously attributed exclusively to B7-1 and B7-2 and have important implications in therapeutic interventions against human diseases.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Sheng
authors.initials: S
authors.lastname: Yao
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Zhu
authors.forename: Gefeng
authors.initials: G
authors.lastname: Zhu
authors.forename: Mathew
authors.initials: M
authors.lastname: Augustine
authors.forename: Linghua
authors.initials: L
authors.lastname: Zheng
authors.forename: Diana J
authors.initials: DJ
authors.lastname: Goode
authors.forename: Megan
authors.initials: M
authors.lastname: Broadwater
authors.forename: William
authors.initials: W
authors.lastname: Ruff
authors.forename: Sarah
authors.initials: S
authors.lastname: Flies
authors.forename: Haiying
authors.initials: H
authors.lastname: Xu
authors.forename: Dallas
authors.initials: D
authors.lastname: Flies
authors.forename: Liqun
authors.initials: L
authors.lastname: Luo
authors.forename: Shengdian
authors.initials: S
authors.lastname: Wang
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001665:Binding Sites; D018106:CD28 Antigens / Q000737:chemistry / Q000276:immunology*; D060908:CTLA-4 Antigen; D002460:Cell Line; D049109:Cell Proliferation; D006801:Humans; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D020836:Protein Structure, Quaternary; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; C556692:ICOS protein, human; C498514:ICOSLG protein, human; C556694:Icos protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D008024:Ligands