Abstract

Lateral mobility and organization of cell surface molecules are important in normal cell functions, for example, response of receptors to their ligands and presentation of antigens to T cells. Even the general principles of lateral organization of membranes are not well understood. Our work concentrates on the mobility and associations of class I MHC antigens. These properties of the antigens appear to be affected by the organization of membranes into domains, and by the extent of glycosylation of membrane proteins. We will characterize lateral diffusion of the antigens in glycosylation-defective mutant cells and will use both fluorescence photobleaching and digital video microscopy to characterize the spatial organization of a variety of class I antigens in fibroblasts and lymphocytes. We will use flow cytometric measurements of quenching of Terbium-labeled antibodies to determine local diffusion coefficients and to select variants in lateral diffusion for function studies. The function of class I antigens in antigen presentation will be investigated by measuring energy transfer between class I antigens labeled with fluorescent beta-2m and fluorescent viral antigens. Differences in the mobility of class I antigens in different lymphocyte subsets will also be investigated.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI014584-25
Application #
3480785
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1978-01-01
Project End
1992-12-31
Budget Start
1991-01-01
Budget End
1991-12-31
Support Year
25
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Type
Schools of Arts and Sciences
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Boyle, Sarah; Kolin, David L; Bieler, Joan Glick et al. (2011) Quantum dot fluorescence characterizes the nanoscale organization of T cell receptors for antigen. Biophys J 101:L57-9
Edidin, Michael (2010) Class I MHC molecules as probes of membrane patchiness: from biophysical measurements to modulation of immune responses. Immunol Res 47:265-72
Abe, Fumiyoshi; Van Prooyen, Nancy; Ladasky, John J et al. (2009) Interaction of Bap31 and MHC class I molecules and their traffic out of the endoplasmic reticulum. J Immunol 182:4776-83
Fooksman, David Robert; Shaikh, Saame Raza; Boyle, Sarah et al. (2009) Cutting edge: phosphatidylinositol 4,5-bisphosphate concentration at the APC side of the immunological synapse is required for effector T cell function. J Immunol 182:5179-82
Shaikh, S R; Mitchell, D; Carroll, E et al. (2008) Differential effects of a saturated and a monounsaturated fatty acid on MHC class I antigen presentation. Scand J Immunol 68:30-42
Lavi, Yael; Edidin, Michael A; Gheber, Levi A (2007) Dynamic patches of membrane proteins. Biophys J 93:L35-7
Everett, Maya W; Edidin, Michael (2007) Tapasin increases efficiency of MHC I assembly in the endoplasmic reticulum but does not affect MHC I stability at the cell surface. J Immunol 179:7646-52
Shaikh, Saame Raza; Edidin, Michael (2007) Immunosuppressive effects of polyunsaturated fatty acids on antigen presentation by human leukocyte antigen class I molecules. J Lipid Res 48:127-38
Suzuki, Kenichi G N; Fujiwara, Takahiro K; Edidin, Michael et al. (2007) Dynamic recruitment of phospholipase C gamma at transiently immobilized GPI-anchored receptor clusters induces IP3-Ca2+ signaling: single-molecule tracking study 2. J Cell Biol 177:731-42
Suzuki, Kenichi G N; Fujiwara, Takahiro K; Sanematsu, Fumiyuki et al. (2007) GPI-anchored receptor clusters transiently recruit Lyn and G alpha for temporary cluster immobilization and Lyn activation: single-molecule tracking study 1. J Cell Biol 177:717-30

Showing the most recent 10 out of 52 publications