The goal of these studies is to understand the basic molecular mechanisms that govern the initial recognition events in the immune response. As examples of these, we have focused on the interaction of the MHC class I molecule, complexed with self or viral peptides, with the T cell receptor, or with a receptor on natural killer cells, Ly-49. We have developed model systems for the study of this interaction both with purified protein molecules as well as with cellular T cell responses. Major accomplishments during the past year include: 1) development of a bacterial expression system in which a three domain T cell receptor is produced that maintains biochemical and immunological integrity, and in which biophysical parameters of binding parallel the biological activity of the molecule; 2) demonstration of the utility of such a three domain T cell receptor for specific blocking of T cell activation; 3) refinement of methodologies for the precise measurement of TCR/MHC/peptide interactions; 4) evaluation of the role of specific peptides in the interaction of the mouse MHC class I molecule H-2Dd with the NK cell receptor Ly-49A.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000394-13
Application #
2566765
Study Section
Special Emphasis Panel (LI)
Project Start
Project End
Budget Start
Budget End
Support Year
13
Fiscal Year
1996
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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