7 205

Cited 6 times in

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

Authors
Kwon, YS; Chung, J; Shin, GT; Lee, SY; Jang, YJ
Citation
Molecular immunology, 42(3):311-317, 2005
Journal Title
Molecular immunology
ISSN
0161-58901872-9142
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.
MeSH terms
Amino Acid SequenceAntibodies, Monoclonal/genetics*Antibodies, Monoclonal/immunologyAutoantibodies/genetics*Autoantibodies/immunologyHistones/immunology*HumansImmunoblottingImmunoglobulin Fab Fragments/analysisImmunoglobulin Fab Fragments/immunologyImmunoglobulin Variable Region/genetics*Lupus Erythematosus, Systemic/geneticsLupus Erythematosus, Systemic/immunology*Molecular Sequence DataPeptide Library
DOI
10.1016/j.molimm.2004.07.008
PMID
15589319
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Nephrology
Journal Papers > School of Medicine / Graduate School of Medicine > Pediatrics & Adolescent Medicine
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
AJOU Authors
신, 규태이, 수영장, 영주
Full Text Link
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse