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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Harvard University
Schools of Arts and Sciences
United States
Zip Code
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
Strominger, J L (1987) Structure of class I and class II HLA antigens. Br Med Bull 43:81-93
Rojo, S; Aparicio, P; Hansen, J A et al. (1987) Structural analysis of an HLA-B27 functional variant, B27d, detected in American blacks. J Immunol 139:3396-401
Rojo, S; Aparicio, P; Choo, S Y et al. (1987) Structural analysis of an HLA-B27 population variant, B27f. Multiple patterns of amino acid changes within a single polypeptide segment generate polymorphism in HLA-B27. J Immunol 139:831-6

Showing the most recent 10 out of 33 publications