Molecular complexes between antigenic peptides and proteins of the Major Histocompatibility Complex play a key role in immunological discrimination between self and non-self This research entails studies of the kinetics of reactions between class II MHC proteins and peptides, with particular reference to the formation of isomers of these complexes. The class II proteins to be studied included water soluble constructs of murine E(k) and human DR molecules. The peptides are generally tagged with fluorescent groups for high sensitivity detection, or fluorine atoms for NMR spectroscopy. It is theoretically possible that defects in the discrimination between self and non-self lead to autoimmune disease, and that such defects may sometimes be related to the adventitious formation of isomers of class II-MHC peptide complexes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI013587-25
Application #
6149745
Study Section
Special Emphasis Panel (ZRG3-BBCB (04))
Program Officer
Deckhut Augustine, Alison M
Project Start
1994-05-01
Project End
2003-01-31
Budget Start
2000-02-01
Budget End
2001-01-31
Support Year
25
Fiscal Year
2000
Total Cost
$348,244
Indirect Cost
Name
Stanford University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Vrljic, Marija; Nishimura, Stefanie Y; Moerner, W E et al. (2005) Cholesterol depletion suppresses the translational diffusion of class II major histocompatibility complex proteins in the plasma membrane. Biophys J 88:334-47
Belmares, Michael P; Busch, Robert; Mellins, Elizabeth D et al. (2003) Formation of two peptide/MHC II isomers is catalyzed differentially by HLA-DM. Biochemistry 42:838-47
Hall, Frances C; Visconti, Kevin C; Ahmad, Regina-Celeste et al. (2003) Cytokines elicited by T cell epitopes from a synovial autoantigen: altered peptide ligands can reduce interferon-gamma and interleukin-10 production. Arthritis Rheum 48:2375-85
McConnell, Harden M; Vrljic, Marija (2003) Liquid-liquid immiscibility in membranes. Annu Rev Biophys Biomol Struct 32:469-92
McConnell, Harden M; Radhakrishnan, Arun (2003) Condensed complexes of cholesterol and phospholipids. Biochim Biophys Acta 1610:159-73
Hall, Frances C; Rabinowitz, Joshua D; Busch, Robert et al. (2002) Relationship between kinetic stability and immunogenicity of HLA-DR4/peptide complexes. Eur J Immunol 32:662-70
Belmares, Michael P; Busch, Robert; Wucherpfennig, Kai W et al. (2002) Structural factors contributing to DM susceptibility of MHC class II/peptide complexes. J Immunol 169:5109-17
Vrljic, Marija; Nishimura, Stefanie Y; Brasselet, Sophie et al. (2002) Translational diffusion of individual class II MHC membrane proteins in cells. Biophys J 83:2681-92
Radhakrishnan, Arun; McConnell, Harden M (2002) Critical points in charged membranes containing cholesterol. Proc Natl Acad Sci U S A 99:13391-6
Anderson, Thomas G; McConnell, Harden M (2002) A thermodynamic model for extended complexes of cholesterol and phospholipid. Biophys J 83:2039-52

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