Abstract

The molecular mechanism by which the superantigen that causes Toxic Shock Syndrome, TSST-l, binds to human class II histocompatibility antigen and T-cell receptors will be studied by high resolution X-ray crystallography. A complex between a soluble form of the class II MHC molecule HLA-DR1 will be crystallized in complex with TSST-l and selected subfragments. A soluble form of alpha-beta T-cell receptor (TCR) that interacts with TSST- l will be constructed and attempts made to form and to crystallize the ternary complex DR1:TSST-1:TCR. A strategy is also proposed for discovering and constructing a soluble form of a gamma-delta TCR that interacts with TSST-1. If successful, this might allow the structure determination of a gamma-delta TCR in an active complex (DR1:TSST-1: gamma-delta TCR).

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD017461-14
Application #
6240938
Study Section
Project Start
1997-04-01
Project End
1998-03-31
Budget Start
1996-10-01
Budget End
1997-09-30
Support Year
14
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Immune Disease Institute, Inc.
Department
Type
DUNS #
115524410
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Szilagyi, Agnes; Banlaki, Zsofia; Pozsonyi, Eva et al. (2010) Frequent occurrence of conserved extended haplotypes (CEHs) in two Caucasian populations. Mol Immunol 47:1899-904
Johnson, B A; Geha, M; Blackwell, T K (2000) Similar but distinct effects of the tristetraprolin/TIS11 immediate-early proteins on cell survival. Oncogene 19:1657-64
Libert, C; Wielockx, B; Grijalba, B et al. (1999) The role of complement activation in tumour necrosis factor-induced lethal hepatitis. Cytokine 11:617-25
Circolo, A; Garnier, G; Fukuda, W et al. (1999) Genetic disruption of the murine complement C3 promoter region generates deficient mice with extrahepatic expression of C3 mRNA. Immunopharmacology 42:135-49
Lokki, M L; Circolo, A; Ahokas, P et al. (1999) Deficiency of human complement protein C4 due to identical frameshift mutations in the C4A and C4B genes. J Immunol 162:3687-93
De, J; Lai, W S; Thorn, J M et al. (1999) Identification of four CCCH zinc finger proteins in Xenopus, including a novel vertebrate protein with four zinc fingers and severely restricted expression. Gene 228:133-45
Hausmann, S; Biddison, W E; Smith, K J et al. (1999) Peptide recognition by two HLA-A2/Tax11-19-specific T cell clones in relationship to their MHC/peptide/TCR crystal structures. J Immunol 162:5389-97
Wang, X; Circolo, A; Lokki, M L et al. (1998) Molecular heterogeneity in deficiency of complement protein C2 type I. Immunology 93:184-91
Gauthier, L; Smith, K J; Pyrdol, J et al. (1998) Expression and crystallization of the complex of HLA-DR2 (DRA, DRB1*1501) and an immunodominant peptide of human myelin basic protein. Proc Natl Acad Sci U S A 95:11828-33
Tsitsikov, E N; Gutierrez-Ramos, J C; Geha, R S (1997) Impaired CD19 expression and signaling, enhanced antibody response to type II T independent antigen and reduction of B-1 cells in CD81-deficient mice. Proc Natl Acad Sci U S A 94:10844-9

Showing the most recent 10 out of 61 publications