H-chain CDR3 contribution in specificity of autoantibodies

Excerpt

Systemic lupus erythematosus is characterized by the production of antibodies directed against various nuclear antigens. Many groups have focused on the sequence of the V region genes of antinuclear antibodies and several features accounting for DNA binding have emerged from these sequences, especially in VH-CDR (H3). In this study, the authors exchanged H3 domains between the 3H9 antibody and two donor antibodies, LG8-1 (closely related to 3H9) and ASWA1 (divergent from 3H9). The H3 domain of these three antibodies differed in the number of arginine residues and in overall charge and these antibodies share different specificities. Variant H chains were expressed together with the 3H9 light chain as single-chain Fv (scFv), and the five antibodies were then tested for their ability to bind nucleosomes, DNA and cardiolipin. …