Abstract

The focus of this work has been to understand the molecular details that control the interaction of MHC molecules with NK receptors, T cell receptors, and with coreceptors such as CD8. These studies are dependent upon structural, functional, and biophysical analysis of the interaction of the molecules in question, and attempts are made to correlate binding properties with function and structure. Progress in the past year has been particularly fruitful with respect to: 1) the binding analysis of a large panel of MHC-I, beta2-microglobulin, and NK receptor (Ly49A) site directed mutants that identify the major site of interaction to a large region that includes residues both of the MHC and of the beta2-m light chain; and 2) binding studies of Ly49C with H-2Kb. These studies have resolved a major controversy concerning the site of interaction of the murine lectin-like NK receptors with MHC-I and raise additional questions as to how receptors with limited, but degenerate specificity function. In addition, the determination of the X-ray structure of the NK receptor, Ly49I, which has distinct specificity from Ly49C and Ly49A offers a glimpse of the plasticity of these molecules. Crystals obtained from complexes of H-2Kb with Ly49C suggest that a structure determination of this distinct MHC/receptor complex may be in sight.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000622-11
Application #
6669526
Study Section
(LI)
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2002
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
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