Anti-β2-glycoprotein-I antibodies in scFv format

Phage display was introduced almost 20 years ago. It has been used to produce large amounts of diverse proteins, to analyze protein–ligand interactions, to improve the affinity of proteins for their binding receptors, and to characterize antibody binding sites. The recombinant version of the antibody Fv is termed single-chain variable fragment (scFv). Many large phage libraries have been developed that have yielded antibodies to several hundred antigens, but only 5 human anti-β2-glycoprotein-I and three anti-prothrombin antibodies in scFV have been so far characterized. Antibodies to β2GP-I thus generated show 92–94% homology with their nearest germ line genes. Their mutations frequently appear to be independent of antigen. Two anti-prothrombin antibodies show strong crossreactivity with β2GP-I. Four mouse anti-β2GP-I scFV show less binding properties than their original counterparts, but had the same capacity of inducing experimental antiphospholipid syndrome. This pathogenicity appears to reside in the VHDJHCH region of the scFv since the VHDJHCH regions of pathogenic scFV combined with irrelevant VL JLCL regions retained their pathogenicity while the opposite failed to do so.