Abstract

The mechanisms by which human receptors for immunoglobulin G constant regions (Fcgamma receptors) effect intracellular signal transduction will be studied by an approach emphasizing the use of recombinant vaccinia viruses to deliver genes encoding the receptors or receptor chimeras to functional effector cells. The receptor chimeras will be formed by genetic fusion of sequences encoding the extracellular domains of different leukocyte surface antigens to the transmembrane and intracellular sequences of human Fc receptors. Using cytolysis assays which depend on the ability of cells bearing Fc receptors to recognize and destroy antibody coated target cells, or which depend on the ability of cells bearing Fc receptor chimeras to recognize and destroy hybridoma cells expressing surface antibody binding to the extracellular portion of the chimera, we will investigate the Fc receptor sequences required for effective cytolysis, as well as the ability of different hematopoietic cell types to carry out cytolysis mediated by the different receptor isoforms.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI027849-06
Application #
2064138
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1989-06-01
Project End
1997-05-31
Budget Start
1994-06-01
Budget End
1995-05-31
Support Year
6
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199

  Publications

Adams, J C; Seed, B; Lu, N et al. (2009) Selective activation of nuclear factor kappa B in the cochlea by sensory and inflammatory stress. Neuroscience 160:530-9
Medoff, Benjamin D; Seed, Brian; Jackobek, Ryan et al. (2006) CARMA1 is critical for the development of allergic airway inflammation in a murine model of asthma. J Immunol 176:7272-7
Xavier, Ramnik; Rabizadeh, Shahrooz; Ishiguro, Kazuhiro et al. (2004) Discs large (Dlg1) complexes in lymphocyte activation. J Cell Biol 166:173-8
Yang, Yi; Seed, Brian (2003) Site-specific gene targeting in mouse embryonic stem cells with intact bacterial artificial chromosomes. Nat Biotechnol 21:447-51
Lichtenthaler, Stefan F; Dominguez, Diana-Ines; Westmeyer, Gil G et al. (2003) The cell adhesion protein P-selectin glycoprotein ligand-1 is a substrate for the aspartyl protease BACE1. J Biol Chem 278:48713-9
Yang, Y; Kuang, Y; Montes De Oca, R et al. (2001) Targeted disruption of the murine Fanconi anemia gene, Fancg/Xrcc9. Blood 98:3435-40
Beck, P L; Xavier, R; Lu, N et al. (2000) Mechanisms of NSAID-induced gastrointestinal injury defined using mutant mice. Gastroenterology 119:699-705
Pimentel-Muinos, F X; Seed, B (1999) Regulated commitment of TNF receptor signaling: a molecular switch for death or activation. Immunity 11:783-93
Xavier, R; Brennan, T; Li, Q et al. (1998) Membrane compartmentation is required for efficient T cell activation. Immunity 8:723-32
Fukumura, D; Xavier, R; Sugiura, T et al. (1998) Tumor induction of VEGF promoter activity in stromal cells. Cell 94:715-25

Showing the most recent 10 out of 19 publications