The objective of this work has been to understand the details of the interaction of self and foreign antigenic peptides with the MHC class I molecule by detailed kinetic and equilibrium binding methods. In addition to allowing us to understand the underlying biochemical rules that govern protein/peptide interactions, these studies provide specific information on particular MHC/peptide interactions which govern the initiation of the immune response. In the past year we have further improved upon quantitative assays, examined a number of protein/peptide interactions, including antibody/peptide interactions. Understanding these processes on a biochemical and biophysical level provides a basis not only for understanding the binding reactions, but also offers an opportunity for rational design of peptide analogs that might be useful in immunization and intervention in autoimmune disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000622-05
Application #
2566827
Study Section
Special Emphasis Panel (LI)
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1996
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Margulies, David H (2009) Antigen-processing and presentation pathways select antigenic HIV peptides in the fight against viral evolution. Nat Immunol 10:566-8
Dzutsev, Amiran K; Belyakov, Igor M; Isakov, Dmitry V et al. (2008) Estimation of low frequency antigen-presenting cells with a novel RELISPOT assay. J Immunol Methods 333:71-8
Belyakov, Igor M; Kozlowski, Steven; Mage, Michael et al. (2007) Role of alpha3 domain of class I MHC molecules in the activation of high- and low-avidity CD8+ CTLs. Int Immunol 19:1413-20
Dzutsev, Amiran H; Belyakov, Igor M; Isakov, Dmitry V et al. (2007) Avidity of CD8 T cells sharpens immunodominance. Int Immunol 19:497-507
Mans, Janet; Natarajan, Kannan; Balbo, Andrea et al. (2007) Cellular expression and crystal structure of the murine cytomegalovirus major histocompatibility complex class I-like glycoprotein, m153. J Biol Chem 282:35247-58
Natarajan, Kannan; Hicks, Ashleigh; Mans, Janet et al. (2006) Crystal structure of the murine cytomegalovirus MHC-I homolog m144. J Mol Biol 358:157-71
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
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
Margulies, David H (2003) Molecular interactions: stiff or floppy (or somewhere in between?). Immunity 19:772-4
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

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