The longterm objective of this research plan is to improve our understanding of the genetic specificity of immune recognition and of responses to major and minor histocompatibility antigens and to MHC-restricted antigens. We will use four approaches to determine the extent of serologically detectable genetic polymorphism within the human major histocompatibility complex (MHC): a.) to compare serologic reaction patterns of different ethnic and hybrid populations to identify antigenic variants, b.) to extensively characterize allo, xeno and monoclonal antibodies in order to identify definitive reagents for polymorphic allodeterminants, c.) to investigate whether serologically defined HLA-A and B allodeterminants are also recognized by cytotoxic lymphocytes and d.) to identify serologic and cellular reagents that distinguish different MHC class II subsets. A variety of serologic and cellular approaches will be taken to determine within the human genome, the identify and location of non-MHC linked histocompatibility antigens which induce acute allograft rejection and severe graft versus host disease in recipients of genotypically MHC identical allografts. Family studies will be carried out to confirm the mode of inheritance of new minor and major allodeterminants, and in recombinant families, to map genes within the MHC complex. Evidence for gene complementation leading to specific unresponsiveness in mixed lymphocyte reactions will be sought. We will investigate the genetic bases for significant associations between the MHC complex and certain diseases; namely idiopathic hemochromatosis and malaria. We will extend existing methodology for genetic analyses of human disorders, particularly those with delayed onset and multiple modes of expression, qualities characteristic of many immunologic disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM010356-23
Application #
3268097
Study Section
Immunobiology Study Section (IMB)
Project Start
1974-10-01
Project End
1987-02-28
Budget Start
1986-03-01
Budget End
1987-02-28
Support Year
23
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Yi, Feng; DeCan, Evan; Stoll, Kurt et al. (2015) Muscarinic excitation of parvalbumin-positive interneurons contributes to the severity of pilocarpine-induced seizures. Epilepsia 56:297-309
Stierle, Andrea A; Stierle, Donald B; Girtsman, Teri et al. (2015) Azaphilones from an Acid Mine Extremophile Strain of a Pleurostomophora sp. J Nat Prod 78:2917-23
McClelland, Levi J; Mou, Tung-Chung; Jeakins-Cooley, Margaret E et al. (2014) Structure of a mitochondrial cytochrome c conformer competent for peroxidase activity. Proc Natl Acad Sci U S A 111:6648-53
Hall, R P; Ward, F E; Wenstrup, R J (1990) An HLA class II region restriction fragment length polymorphism (RFLP) in patients with dermatitis herpetiformis: association with HLA-DP phenotype. J Invest Dermatol 95:172-7
Hall, R P; Clark, R E; Ward, F E (1990) Dermatitis herpetiformis in two American blacks: HLA type and clinical characteristics. J Am Acad Dermatol 22:436-9
Brissette-Storkus, C S; Kostyu, D D; Boyer, C M et al. (1990) Induction of HLA-specific CTL to nonimmunogenic, heat-inactivated lymphocytes by interleukin 2. Transplantation 50:862-9
Markert, M L; Norby-Slycord, C; Ward, F E (1989) A high proportion of ADA point mutations associated with a specific alanine-to-valine substitution. Am J Hum Genet 45:354-61
Ward, F E; Stewart, A D; Ruiz, R E et al. (1989) Epitopes within the HLA-B5,B35 cross-reacting group. Hum Immunol 26:151-67
Ward, F E; Jensen, J B; Abdul Hadi, N H et al. (1989) HLA genotypes and variant alleles in Sudanese families of Arab-Negroid tribal origin. Hum Immunol 24:239-51
Carrington, M N; Tharp-Hiltbold, B; Knoth, J et al. (1988) 1,25-Dihydroxyvitamin D3 decreases expression of HLA class II molecules in a melanoma cell line. J Immunol 140:4013-8

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