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Variable region genes of human monoclonal autoantibodies to histones H2A and H2B from a systemic lupus erythematosus patient

Cited 6 time in Web of Science Cited 7 time in Scopus
Authors
Kwon, Yong Soon; Chung, Junho; Shin, Gyu Tae; Lee, Soo Young; Jang, Young-Ju
Issue Date
2005
Publisher
Elsevier
Citation
Molecular Immunology 42, 311-317
Keywords
Amino Acid SequenceAntibodies, Monoclonal/*genetics/immunologyAutoantibodies/*genetics/immunologyHistones/*immunologyHumansImmunoblottingImmunoglobulin Fab Fragments/analysis/immunologyImmunoglobulin Variable Region/*geneticsLupus Erythematosus, Systemic/genetics/*immunologyMolecular Sequence DataPeptide Library
Abstract
An antibody phage library obtained from peripheral blood lymphocytes of a systemic lupus erythematosus (SLE) patient was used to isolate four monoclonal autoantibodies against histones H2A and H2B. Analysis of the variable region sequences revealed that the anti-histone monoclonal antibodies were not clonally related; they used VH genes from three different VH gene families (VH3, VH4, and VH5) and distant members of the Vkappa group (L25, L6, A27, and O8) in conjunction with different D and J gene segments. These observations suggest that certain gene families or segments are not critical in producing anti-histone autoantibodies in SLE. Most of the utilized VH and Vkappa sequences were highly mutated and the complementarity-determining regions (CDRs) varied greatly in length. The VH region of the antibody SLEhis18 had an isoelectric point of 6.1, and 29% of the mutations were changes to acidic amino acid residues. The second CDR (CDR2) of SLEhis18 VH contained one basic and three acidic residues. Acidic residues were observed in the CDR3 regions of VH, but not VL, in all isolated clones; this is unusual, as most autoantibodies are comprised predominantly of non-acidic residues. This is the first report of a systematic sequence analysis of human anti-histone monoclonal antibodies. Our results suggest that certain V genes are not important for autoreactive specificity to histones in SLE; instead, other mechanisms such as an existence of acidic residues and somatic mutations in CDRs are required for specific binding to histones, which might play a role as a stimulatory autoantigen for the activation of autoantibody-producing B-cells and the selection of high affinity antibody.
ISSN
0161-5890 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15589319

http://hdl.handle.net/10371/27831
DOI
https://doi.org/10.1016/j.molimm.2004.07.008
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biochemistry & Molecular Biology (생화학교실)Journal Papers (저널논문_생화학교실)
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