The proposed studies were designed to provide a molecular analysis of structure, organization and polymorphisms of genes within the major histocompatibility complex (MHC) on the short arm of chromosome six (6p) and particularly as they relate to disease states and the normal immune response. Superantigens (bacterial toxins of S. aureus) will be cocrystallized with MHC class II molecules to define how these toxins bind to MHC class II molecules. Gene targeting experiments will be performed to eliminate genes of factor B and the complement component C4 to define further the role of MHC class III molecules in the normal immune response. findings from studies of polymorphisms of MHC molecules will be applied to disease associations, particularly to defining the MHC association of common variable immunodeficiency (CVID). Modern tools of molecular genetics, protein biosynthesis and protein chemistry will be applied to the study of patients, their families and normal families with informative markers on 6p. The overall objective of this project is an understanding of diseases associated with the MHC and the finding of predictive independent markers for these disorders. Thus, more effective and comprehensive diagnosis, genetic counselling and treatment strategies might result.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD017461-12
Application #
2197455
Study Section
Special Emphasis Panel (SRC (FR))
Project Start
1983-04-01
Project End
1999-03-31
Budget Start
1995-04-01
Budget End
1996-03-31
Support Year
12
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Immune Disease Institute, Inc.
Department
Type
DUNS #
115524410
City
Boston
State
MA
Country
United States
Zip Code
02115
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

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