Abstract

This proposal aims at characterizing the structural and functional properties of the gene products of the various loci of the human I region and at identifying the corresponding receptors on alloactivated T cells. Human and murine monoclonal antibodies to distinct domains of Ia antigens will be developed using several immunization procedures and characterized with a combination of serological and immunochemical assays. Antibodies will be used to analyze the molecular organization of the gene products of the I region and the structural relationship among the antigenic series identified with alloantisera in the Ia system. Antibodies will be used to probe the function of distinct domains of Ia antigens in cell-cell interactions. The clinical significance of these findings will be assessed by determining the association between determinants recognized by monoclonal antibodies and susceptibility to disease. Monoclonal antibodies to Ia allospecificities will be used to elicit antiidiotypic xenoantisera and monoclonal antibodies. These reagents will be evaluated for their effect on cell-cell interactions and to quantitate alloreactive T cells in subjects exposed to the appropriate Ia allospecificity. The clinical significance of this approach will be assessed by correlating the number of alloreactive T cells in kidney allograft recipients with the clinical course of the disease. Antiidiotype antibodies may eventually be used to manipulate specific immune responses in organ transplantation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI021384-02
Application #
3131439
Study Section
Immunobiology Study Section (IMB)
Project Start
1983-12-01
Project End
1986-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
New York Medical College
Department
Type
Schools of Medicine
DUNS #
City
Valhalla
State
NY
Country
United States
Zip Code
10595

  Publications

Volk, H; Charlemagne, J; Tournefier, A et al. (1998) Wide tissue distribution of axolotl class II molecules occurs independently of thyroxin. Immunogenetics 47:339-49
Armandola, E A; Mariani, S M; Ferrone, S (1993) Serological and molecular characterization of mouse anti-idiotypic monoclonal antibodies elicited with the syngeneic anti-HLA-A2,28 monoclonal antibody CR11-351. Mol Immunol 30:287-300
Mariani, S M; Armandola, E A; Ferrone, S (1993) Preferential selection of a subset of anti-HLA-DR monoclonal antibodies by a syngeneic antiidiotypic monoclonal antibody. Transplantation 55:1176-81
Temponi, M; Kekish, U; Hamby, C V et al. (1993) Characterization of anti-HLA class II monoclonal antibody LGII-612.14 reacting with formalin fixed tissues. J Immunol Methods 161:239-56
Mariani, S M; Armandola, E A; Ferrone, S (1992) Heterogeneity in the anti-HLA-DR immune response elicited by the antiidiotypic monoclonal antibody F5-444. Analysis at the clonal level. Transplantation 54:1078-84
Mariani, S M; Armandola, E A; Ferrone, S (1992) Diversity of anti-HLA-DR antibodies elicited by distinct anti-idiotypic monoclonal antibodies recognizing idiotopes co-expressed by the immunizing monoclonal antibody. Immunology 77:597-603
Kageshita, T; Ono, T; Hirai, S et al. (1992) Ganglioside, adhesion molecule, and HLA antigen expression in basal cell carcinoma lesions. Cancer Res 52:3201-7
Armandola, E A; Mariani, S M; Zwickl, M et al. (1992) Molecular analysis of anti-idiotypic monoclonal antibodies in the HLA-DR antigenic system. Eur J Immunol 22:2893-9
Cozzi, E; Ferrone, S (1992) Immunotherapeutic approaches with monoclonal antibodies to immunological diseases. Recenti Prog Med 83:528-33
D'Urso, C M; Wang, Z G; Cao, Y et al. (1991) Lack of HLA class I antigen expression by cultured melanoma cells FO-1 due to a defect in B2m gene expression. J Clin Invest 87:284-92

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