Abstract

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. These studies permit us to understand the underlying biochemical rules that govern peptide/protein interactions, as well as how MHC molecules bind peptides both in intracellular compartments as well as the cell surface. In the past year we have further developed quantitative assays and have examined a number of peptide/MHC as well as several peptide antibody interactions. Understanding these processes on a biochemical and biophysical level provides a basis not only for understanding how MHC molecules bind and select self and antigenic peptides, but also offers an opportunity for rational design of peptide analogs for both immunization and for intervention in autoimmune disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000622-04
Application #
5200530
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

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
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

Showing the most recent 10 out of 31 publications