Abstract

The specific aims of this project are to isolate the polymorphic human histocompatibility antigens (the products of the HLA-A, -B, -C and -D/DR genes in the Major Histocompatibility Complex (MHC) and to elucidate their structures. The molecles which will be studied include HLA-A2, -A28, -B27, -B40, -Cw1, -Cw3, -DRw6 and -DRw8. One of these (HLA-B27) has a very strong association with a human disease. Of special importance is the nature of the alloantigenic site(s) in these molecules which are recognized by alloantibodies and various immune cells such as allo or modified self directed cytolytic T cells. The MHC antigens also mediate various other cell-cell interactions in the immune system. The isolated molecules as well as the structural information about them will be employed in studies of the functions of the molecules. In particular, we wish to explore in as much detail as possible the cytolytic T-cell response both to HLA-A, -B and -C antigens and to HLA-DR antigens and to these antigens modified by chemical means or by interaction with viral antigens. Finally, we hope to use the structural information acquired about these molecules to learn more about how membrane proteins are organized and integrated with cell function.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI010736-11
Application #
3124804
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1976-02-01
Project End
1986-06-30
Budget Start
1985-02-01
Budget End
1986-06-30
Support Year
11
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Harvard University
Department
Type
Schools of Arts and Sciences
DUNS #
071723621
City
Cambridge
State
MA
Country
United States
Zip Code

  Publications

Pioli, P A; Rigby, W F (2001) The von Hippel-Lindau protein interacts with heteronuclear ribonucleoprotein a2 and regulates its expression. J Biol Chem 276:40346-52
Groh, V; Porcelli, S; Fabbi, M et al. (1989) Human lymphocytes bearing T cell receptor gamma/delta are phenotypically diverse and evenly distributed throughout the lymphoid system. J Exp Med 169:1277-94
Gorga, J C; Dong, A; Manning, M C et al. (1989) Comparison of the secondary structures of human class I and class II major histocompatibility complex antigens by Fourier transform infrared and circular dichroism spectroscopy. Proc Natl Acad Sci U S A 86:2321-5
Sleckman, B P; Peterson, A; Foran, J A et al. (1988) Functional analysis of a cytoplasmic domain-deleted mutant of the CD4 molecule. J Immunol 141:49-54
Domenech, N; Ezquerra, A; Castano, R et al. (1988) Structural analysis of HLA-A2.4 functional variant KNE. Implications for the mapping of HLA-A2-specific T-cell epitopes. Immunogenetics 27:196-202
Castano, R; Ezquerra, A; Domenech, N et al. (1988) An HLA-A2 population variant with structural polymorphism in the alpha 3 region. Immunogenetics 27:345-55
Kappes, D; Strominger, J L (1988) Human class II major histocompatibility complex genes and proteins. Annu Rev Biochem 57:991-1028
Gorga, J C; Horejsi, V; Johnson, D R et al. (1987) Purification and characterization of class II histocompatibility antigens from a homozygous human B cell line. J Biol Chem 262:16087-94
Tanigaki, N; Tosi, R; Strominger, J L et al. (1987) Immunochemistry of the HLA class II molecules isolated from a mouse cell transfected with DQ alpha and beta genes from a DR4 haplotype. Immunogenetics 26:40-7
Strominger, J L (1987) Structure of class I and class II HLA antigens. Br Med Bull 43:81-93

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