title: Structural mechanisms of costimulation.
abstract: Recent studies have highlighted the structural requirements for T cell costimulation and have revealed unusual modes of dimerization for the cytolytic T lymphocyte-associated antigen 4 (CTLA-4) costimulatory receptor and its B7 ligands. These distinctive quaternary structures potentially endow both receptor and ligand with bivalent binding properties, which suggests a number of mechanistic features relevant to signaling. These include the potential to form a highly ordered, alternating network of CTLA-4 and B7 homodimers that may represent the organization of these molecules and their associated signaling partners within the immunological synapse. Primary sequence and structural considerations suggest that some aspects of the organizational and mechanistic features associated with the CTLA-4-B7 complexes may extend to other members of the costimulatory receptor-ligand family. An examination of the signaling mechanisms within the costimulatory receptor-ligand family provides an excellent framework to consider the general principles that are relevant to cell surface receptor-mediated signaling events.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA.
authors.forename: Jean-Claude D
authors.initials: JC
authors.lastname: Schwartz
authors.forename: Xuewu
authors.initials: X
authors.lastname: Zhang
authors.forename: Stanley G
authors.initials: SG
authors.lastname: Nathenson
authors.forename: Steven C
authors.initials: SC
authors.lastname: Almo
mesh_terms: D000069594:Abatacept; D000595:Amino Acid Sequence; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology*; D060908:CTLA-4 Antigen; D006801:Humans; D018796:Immunoconjugates; D008213:Lymphocyte Activation / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D000069594:Abatacept