Abstract

Among HLA Class II antigens HLA-DR4 antigens have been extensively characterized because of their statistically significant, although not absolute, association with insulin dependent diabetes and rheumatoid arthritis. HLA-DR4 antigens indistinguishable with conventional antisera may be associated with structurally distinct HLA-DQw3 antigens, different HLA-D allospecificities and may display structural heterogeneity. Since the available information suggests that subtyping of HLA-DR4 antigens may improve the association with insulin dependent diabetes and with rheumatoid arthritis, this proposal aims at developing monoclonal antibodies which identify subtypes of HLA-DR4 and HLA-DQw3 antigens. Following an extensive characterization the anti HLA-DR4 and anti DQw3 antibodies will be used to develop double determinant immunoassays for HLA Class II typing and to develop antiidiotype antibodies. The latter in turn will be utilized to investigate the modulation of immune response to HLA Class II antigens and to quantitate antiidiotype antibodies in patients with diabetes mellitus and rheumatoid arthritis and in heart and renal transplant recipients. Lymphoid cells and sera will represent the antigen source. Available and newly developed hybridomas will represent the antibody sources. Immunochemical and cell mediated immunity tests will represent the assay systems. The results of these studies will contribute to the characterization of the clinical significance of HLA-DR4 and DQw3 heterogeneity and may suggest novel approaches to treat diseases with autoimmune pathogenesis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI021384-06
Application #
3131442
Study Section
Immunobiology Study Section (IMB)
Project Start
1983-12-01
Project End
1991-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
6
Fiscal Year
1988
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
Mariani, S M; Armandola, E A; Ferrone, S (1991) Diversity in the fine specificity and idiotypic profile of mouse anti-HLA-DR monoclonal antibody elicited with the syngeneic anti-idiotypic monoclonal antibody F5-830. J Immunol 147:1322-30

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