NDLI: Human autoantibody recognition of DNA.

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Human autoantibody recognition of DNA.

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Human autoantibody recognition of DNA.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Salonen, E. M. Yang, W. P. Silverman, G. J. Ditzel, H. J. Barbas, S. M. Burton, D. R.
Description	Author Affiliation: Barbas SM ( Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA.);
Abstract	Combinatorial IgG Fab phage display libraries prepared from a systemic lupus erythematosus (SLE) donor and a healthy donor were affinity selected against human placental DNA. Human monoclonal antibody Fab fragments specific for DNA were isolated from both libraries, although Fabs of the highest affinity were isolated only from the lupus library. Generally, apparent affinities of the Fabs for human placental DNA, purified double-stranded DNA, and denatured DNA were approximately equivalent. Surface plasmon resonance indicated Fab binding constants for a double-stranded oligodeoxynucleotide of 0.2-1.3 x 10(8) M-1. The higher-affinity Fabs, as ranked by binding to human placental DNA or to the oligonucleotide probe, tested positive in the Crithidia luciliae assay commonly used in the diagnosis of SLE, and interestingly the genes encoding the heavy-chain variable regions of these antibodies displayed evidence of only minimal somatic hypermutation. The heavy chains of the SLE Fabs were characterized by a predominance of basic residues toward the N terminus of complementarity-determining region 3 (CDR3). The crucial role of heavy-chain CDR3 (HCDR3) in high-affinity DNA recognition was suggested by the creation of DNA binding in an unrelated antibody by HCDR3 transplantation from SLE antibodies. We propose that high-affinity DNA-binding antibodies can arise in SLE without extensive somatic hypermutation in the variable-region genes because of the expression of inappropriate HCDR3s.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	7
Volume Number	92
Language	English
Publisher	National Academy of Sciences
Publisher Date	1995-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Autoantibodies Immunology DNA HIV Seropositivity Immunoglobulin Fab Fragments Immunoglobulin G Lupus Erythematosus, Systemic Amino Acid Sequence Animals Antibody Affinity Chemistry Enzyme-Linked Immunosorbent Assay Immunoglobulin Heavy Chains Immunoglobulin Light Chains Kinetics Mice Molecular Sequence Data Nucleic Acid Denaturation Oligodeoxyribonucleotides Placenta Pregnancy Receptor-CD3 Complex, Antigen, T-Cell Reference Values Sequence Homology, Amino Acid Transplantation Immunology Comparative Study Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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