Anti-DNA Antibodies - Antigen Binding and Pathogenicity

Diamond, Betty

Abstract

While anti-DNA antibodies are clearly implicated in pathogenesis in the disease systemic lupus erythematosus, some fundamental question about these antibodies remain unanswered. We are just beginning to understand the structural basis for DNA binding. The question will be pursued in two well defined idiotype systems, one murine and one human, using the technique of site directed mutagenesis. Secondly, we will study the structural basis for renal pathogenicity of anti-DNA antibodies. Finally we hope to adapt techniques of bacterial genetics to the generation of somatically mutated antibody genes and to characterize the protein products for idiotypy and antigen binding.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Research Program Projects (P01)
• Project #: 5P01AI033184-02
• Application #: 3769703
• Support Year: 2
• Fiscal Year: 1993

Institution

• Name: Albert Einstein College of Medicine
• DUNS #: 009095365
• City: Bronx
• State: NY
• Country: United States
• Zip Code: 10461

Publications

Valadon, P; Nussbaum, G; Oh, J et al. (1998) Aspects of antigen mimicry revealed by immunization with a peptide mimetic of Cryptococcus neoformans polysaccharide. J Immunol 161:1829-36

Nussbaum, G; Cleare, W; Casadevall, A et al. (1997) Epitope location in the Cryptococcus neoformans capsule is a determinant of antibody efficacy. J Exp Med 185:685-94

Gaynor, B; Putterman, C; Valadon, P et al. (1997) Peptide inhibition of glomerular deposition of an anti-DNA antibody. Proc Natl Acad Sci U S A 94:1955-60

Teller, K; Budhai, L; Zhang, M et al. (1996) HLA-DRB1 and DQB typing of Hispanic American patients with rheumatoid arthritis: the ""shared epitope"" hypothesis may not apply. J Rheumatol 23:1363-8

Valadon, P; Nussbaum, G; Boyd, L F et al. (1996) Peptide libraries define the fine specificity of anti-polysaccharide antibodies to Cryptococcus neoformans. J Mol Biol 261:11-22

Zhu, M; Green, N S; Rabinowitz, J L et al. (1996) Differential V region mutation of two transfected Ig genes and their interaction in cultured B cell lines. EMBO J 15:2738-47

Sakita, I; Horig, H; Sun, R et al. (1996) In vivo CTL immunity can be elicited by in vitro reconstituted MHC/peptide complex. J Immunol Methods 192:105-15

Zhang, M; Spey, D; Ackerman, S et al. (1996) Rheumatoid factor idiotypic and antigenic specificity is strongly influenced by the light chain VJ junction. J Immunol 156:3570-5

Valadon, P; Scharff, M D (1996) Enhancement of ELISAs for screening peptides in epitope phage display libraries. J Immunol Methods 197:171-9

Sun, R; Shepherd, S E; Geier, S S et al. (1995) Evidence that the antigen receptors of cytotoxic T lymphocytes interact with a common recognition pattern on the H-2Kb molecule. Immunity 3:573-82