کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9141664 1163864 2005 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Variable region genes of human monoclonal autoantibodies to histones H2A and H2B from a systemic lupus erythematosus patient
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Variable region genes of human monoclonal autoantibodies to histones H2A and H2B from a systemic lupus erythematosus patient
چکیده انگلیسی
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 Vκ 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 Vκ 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 42, Issue 3, February 2005, Pages 311-317
نویسندگان
, , , , ,