The focus of these studies has been on the functional role of the MHC class I molecule and its interactions with T cell receptors. Model systems have been developed for studies of these functions in vivo and in vitro. Accomplishments during the past year include: 1) quantitative measurement of the interactions between purified T cell receptors and purified MHC class I molecules complexed with a panel of antigenic peptides; 2) engineering of large amounts highly purified T cell receptor domains, and their use for crystallization and functional studies; 3) evaluation of the interaction of soluble H-2Dd with NK cells bearing the Ly-49 surface protein. These studies are providing a new quantitative understanding of the binding interactions between MHC class I-peptide complexes and the receptors of T lymphocytes and NK cells. They may also help produce a detailed structure of the T cell receptor. Together, these investigations will help develop a more complete molecular picture of how immune recognition events involving MHC class I molecules contribute to regulation of the functions of these two important effector cell types.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000394-12
Application #
5200461
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
1995
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Morozov, Giora I; Zhao, Huaying; Mage, Michael G et al. (2016) Interaction of TAPBPR, a tapasin homolog, with MHC-I molecules promotes peptide editing. Proc Natl Acad Sci U S A 113:E1006-15
Margulies, David H (2009) Home schooling of NK cells. Immunity 30:313-5
Hu, Jin-Shan; Plaksin, Daniel; Margulies, David H (2005) Backbone and side chain resonance assignmentsof a TRAV14-3 mouse T cell receptor domain. J Biomol NMR 31:271-2
Margulies, David H (2005) Monoclonal antibodies: producing magic bullets by somatic cell hybridization. J Immunol 174:2451-2
Candon, Sophie; McHugh, Rebecca S; Foucras, Gilles et al. (2004) Spontaneous organ-specific Th2-mediated autoimmunity in TCR transgenic mice. J Immunol 172:2917-24
Kuribayashi, Hideki; Wakabayashi, Ayako; Shimizu, Masumi et al. (2004) Resistance to viral infection by intraepithelial lymphocytes in HIV-1 P18-I10-specific T-cell receptor transgenic mice. Biochem Biophys Res Commun 316:356-63
Dam, Julie; Guan, Rongjin; Natarajan, Kannan et al. (2003) Variable MHC class I engagement by Ly49 natural killer cell receptors demonstrated by the crystal structure of Ly49C bound to H-2K(b). Nat Immunol 4:1213-22
Lukashev, Dmitriy E; Caldwell, Charles C; Chen, Pearl et al. (2003) A serine/threonine phosphorylation site in the ectodomain of a T cell receptor beta chain is required for activation by superantigen. J Recept Signal Transduct Res 23:33-52
Margulies, David H (2003) CD28, costimulator or agonist receptor? J Exp Med 197:949-53
Margulies, David H (2003) Molecular interactions: stiff or floppy (or somewhere in between?). Immunity 19:772-4

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