title: Structure and T cell inhibition properties of B7 family member, B7-H3.
abstract: T cell activity is controlled by a combination of antigen-dependent signaling through the T cell receptor and a set of auxiliary signals delivered through antigen-independent interactions, including the recognition of the B7 family of ligands. B7-H3 is a recently identified B7 family member that is strongly overexpressed in a range of cancers and correlates with poor prognosis. We report the crystal structure of murine B7-H3 at a 3 Å resolution, which provides a model for the organization of the IgV and IgC domains within the ectodomain. We demonstrate that B7-H3 inhibits T cell proliferation and show that the FG loop of the IgV domain plays a critical role in this function. B7-H3 crystallized as an unusual dimer arising from the exchange of the G strands in the IgV domains of partner molecules. This arrangement, in combination with previous reports, highlights the dynamic nature and plasticity of the immunoglobulin fold.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. vladimir.vigdorovich@gmail.com
authors.forename: Vladimir
authors.initials: V
authors.lastname: Vigdorovich
authors.forename: Udupi A
authors.initials: UA
authors.lastname: Ramagopal
authors.forename: Eszter
authors.initials: E
authors.lastname: Lázár-Molnár
authors.forename: Eliezer
authors.initials: E
authors.lastname: Sylvestre
authors.forename: Jun Sik
authors.initials: JS
authors.lastname: Lee
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Hofmeyer
authors.forename: Xingxing
authors.initials: X
authors.lastname: Zang
authors.forename: Stanley G
authors.initials: SG
authors.lastname: Nathenson
authors.forename: Steven C
authors.initials: SC
authors.lastname: Almo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D060887:B7 Antigens / Q000737:chemistry* / Q000378:metabolism; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D004330:Drosophila; D008213:Lymphocyte Activation; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D060887:B7 Antigens; C486038:Cd276 protein, mouse