The importance of somatic mutations in the V(lambda) gene 2a2 in human monoclonal anti-DNA antibodies.

:2a2 is the most commonly rearranged gene in the human V(lambda )locus. It has been postulated that certain immunoglobulin genes (including 2a2) are rearranged preferentially because their germline sequences encode structures capable of binding to a range of antigens. Somatic mutation could then increase the specificity and affinity of binding to a particular antigen. We studied the properties of five IgG molecules in which the same heavy chain was paired with different light chains derived from 2a2. The pattern of somatic mutations in 2a2 was shown to be crucial in conferring the ability to bind DNA, but two different patterns of mutation each conferred this ability.Computer-generated models of the three-dimensional structures of these antibodies illustrate the ability of 2a2 to form a DNA binding site in different ways. Somatic mutations at the periphery of the DNA binding site were particularly important. In two different light chains, mutations to arginine at different sites in the complementarity determining regions (CDRs) enhanced binding to DNA. In a third light chain, however, mutation to arginine at a different site blocked binding to DNA.

Rahman A ，Haley J ，Radway-Bright E ，Nagl S ，Low DG ，Latchman DS ，Isenberg DA ... -  《JOURNAL OF MOLECULAR BIOLOGY》

The critical role of arginine residues in the binding of human monoclonal antibodies to cardiolipin.

Giles I ，Lambrianides N ，Latchman D ，Chen P ，Chukwuocha R ，Isenberg D ，Rahman A ... -  《-》

Structural properties and mutation patterns of anti-nucleosome monoclonal antibodies are similar to those of anti-DNA antibodies.

Brard F ，Jovelin F ，Petit S ，Tron F ，Gilbert D ... -  《EUROPEAN JOURNAL OF IMMUNOLOGY》

Arginine mutation alters binding of a human monoclonal antibody to antigens linked to systemic lupus erythematosus and the antiphospholipid syndrome.

Lambrianides A ，Giles I ，Ioannou Y ，Mason L ，Latchman DS ，Manson JJ ，Isenberg DA ，Rahman A ... -  《ARTHRITIS AND RHEUMATISM》

Autoantibodies, lupus and the science of sabotage.

Rahman A 《RHEUMATOLOGY》