This research seeks to develop and exploit methods for the discovery of molecular events involved in cell-cell recognition, especially among cellular components of the immune system. The techniques employed are those of physical chemistry, membrane biochemistry, and immunology. Immediate objectives include a determination of the kinetic mechanisms for the reactions between antigenic peptides and class 1 as well as class 11 molecules of the major histocompatibility complex (M-molecules). Such reactions are relevant to immune responses to virus infections, such as the killing of virus infected cells by cytotoxic T-lymphocytes, as well as the production of anti-virus antibodies facilitated by helper T-lymphocytes. The physical chemical techniques to be employed include evanescent wave fluorescence microscopy, fluorescence depolarization and NMR. The techniques of molecular biology will be used in an attempt to express class 11 M-molecules in water soluble form for such studies. Biophysical-biochemical experiments on tissue specific lymphocyte homing are also contemplated.

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 #
5R37AI013587-23
Application #
2653790
Study Section
Special Emphasis Panel (NSS)
Project Start
1994-05-01
Project End
1999-01-31
Budget Start
1998-02-01
Budget End
1999-01-31
Support Year
23
Fiscal Year
1998
Total Cost
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
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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
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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Rabinowitz, J D; Rigler, P; Carswell-Crumpton, C et al. (1997) Screening for novel drug effects with a microphysiometer: a potent effect of clofilium unrelated to potassium channel blockade. Life Sci 61:PL87-94
Liang, M N; Lee, C; Xia, Y et al. (1996) Molecular modeling and design of invariant chain peptides with altered dissociation kinetics from class II MHC. Biochemistry 35:14734-42
Mason, K; Denney Jr, D W; McConnell, H M (1995) Kinetics of the reaction of a myelin basic protein peptide with soluble IAu. Biochemistry 34:14874-8
Mason, K; Denney Jr, D W; McConnell, H M (1995) Myelin basic protein peptide complexes with the class II MHC molecules I-Au and I-Ak form and dissociate rapidly at neutral pH. J Immunol 154:5216-27

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