Abstract: Objective To identify the polyreactivity of a monoclonal natural anti-keratin autoantibody 3B4 and to analyze its possible molecularme chanism. Methods enzyme-linked immunosorbent assay (ELISA)and immunohistoche mistry were applied to test the binding reactivity of 3B4 against different antigens and tissues.The variable region genes and their aminoacid composition were sequenced. Results 3B4 could reacted with a range of antigens and tissues,in addition to keratin and skin.The variable region genes of its light chain and heavy chain showed high homology with germline genes VK1 am4 and VH1 J558.42.H CDR3 region,which mainly composed of short side chain amino acids(from 294 to 324 nucleotides around the heavy chain),was the only motif that differs from ot her highly homologous immunoglobulin genes. Conclusions The monoclonal natural anti-keratin autoantibody 3B4,with its variable region genes highly homologo us to germline genes,is highly polyreactive.The flexibility of HCDR3 may contr ibute to the polyreactivity.

Key words: Autoantibodies, Keratin, Antibody specificity