Human autoantibody recognition of DNA.

摘要: Abstract Combinatorial IgG Fab phage display libraries prepared from a systemic lupus erythematosus (SLE) donor and healthy were affinity selected against human placental DNA. Human monoclonal antibody fragments specific for DNA isolated both libraries, although Fabs of the highest only library. Generally, apparent affinities DNA, purified double-stranded denatured approximately equivalent. Surface plasmon resonance indicated binding constants oligodeoxynucleotide 0.2-1.3 x 10(8) M-1. The higher-affinity Fabs, as ranked by to or oligonucleotide probe, tested positive in Crithidia luciliae assay commonly used diagnosis SLE, interestingly genes encoding heavy-chain variable regions these antibodies displayed evidence minimal somatic hypermutation. heavy chains SLE characterized predominance basic residues toward N terminus complementarity-determining region 3 (CDR3). crucial role CDR3 (HCDR3) high-affinity recognition was suggested creation an unrelated HCDR3 transplantation antibodies. We propose that DNA-binding can arise without extensive hypermutation variable-region because expression inappropriate HCDR3s.