Among individuals with the serologically defined HLA-DR7 specificity, six distinct mixed lymphocyte culture (MLC)-defined HLA-D specificities have been described: Dw7, Dw11, Dw17, DW7L, Dw11S, and Dw blank. The family of DR7-associated HLA-D specificities will be used as a system in which to address the long-term objectives of better defining the structure-function relationships of human Ia molecules and the basis for polymorphism generation among Ia molecules. 1. We will determine the structural differences or similarities among Ia genes and the corresponding proteins from cells representing the six DR7-associated HLA-D specificities by constructing cDNA libraries from these cells in the Okayama and Berg expression vector and determining the nucleotide sequences of cDNA clones corresponding to the DR, DQ, and DP alpha and beta chains. 2. We will define the molecular basis for the finding in studies at the protein level that Dw11 homozygous cells express only one DR beta chain by: a) approximating the number of Dw11 DR beta genes using Southern blot analysis, b) analyzing Dw11 DR beta mRNA to determine if an RNA abnormality prevents expression of the DR beta 2 chain, and c) sequencing DR beta genes from a Dw11 genomic library to determine which DR beta gene has been deleted or to identify and characterize the defective gene. 3. We will use DNA-mediated gene transfer of Ia alpha and beta chain cDNAs in the Okayama and Berg expression vector to determine which hybrid DQ molecules and hybrids DP molecules occur and whether mixed-isotype molecules occur in man. The findings of these studies will contribute to the understanding of the diversity of human Ia molecules and the function of immune response genes, which may play important roles in the determination of human health and disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI024138-01A1
Application #
3136837
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1988-07-01
Project End
1993-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Iowa
Department
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Fu, X T; Drover, S; Marshall, W H et al. (1995) HLA-DR residues accessible under the peptide-binding groove contribute to polymorphic antibody epitopes. Hum Immunol 43:243-50
Drover, S; Karr, R W; Fu, X T et al. (1994) Analysis of monoclonal antibodies specific for unique and shared determinants on HLA-DR4 molecules. Hum Immunol 40:51-60
Fu, X T; Karr, R W (1994) HLA-DR alpha chain residues located on the outer loops are involved in nonpolymorphic and polymorphic antibody-binding epitopes. Hum Immunol 39:253-60
Klohe, E; Fu, X T; Ballas, M et al. (1993) HLA-DR beta chain residues that are predicted to be located in the floor of the peptide-binding groove contribute to antibody-binding epitopes. Hum Immunol 37:51-8
Fu, X T; Klohe, E; Alber, C et al. (1992) Diverse locations of amino acids in HLA-DR beta chains involved in polymorphic antibody binding epitopes on DR(alpha, beta 1*0101), DR(alpha, beta 1*1101), and DR(alpha,beta 3*0202) molecules. Hum Immunol 33:193-201
Fu, X T; Yu, W Y; Alber, C et al. (1992) Identification of residues involved in polymorphic antibody binding epitopes on HLA-DR molecules. Hum Immunol 33:47-56
Olson, R R; De Magistris, M T; Di Tommaso, A et al. (1992) Mutations in the third, but not the first or second, hypervariable regions of DR(beta 1*0101) eliminate DR1-restricted recognition of a pertussis toxin peptide. J Immunol 148:2703-8
Klohe, E; Pistillo, M P; Ferrara, G B et al. (1992) Critical role of HLA-DR beta 1 residue 58 in multiple polymorphic epitopes recognized by xenogeneic and allogeneic antibodies. Hum Immunol 35:18-28
Hammond, S A; Obah, E; Stanhope, P et al. (1991) Characterization of a conserved T cell epitope in HIV-1 gp41 recognized by vaccine-induced human cytolytic T cells. J Immunol 146:1470-7
Lee, K W; Johnson, A H; Tang, T et al. (1991) DRw11 haplotypes: continuum of DRB1 diversity augmented by unique DQ/DRw52 associations. Hum Immunol 32:150-5

Showing the most recent 10 out of 19 publications