STRUCTURE AND BINDING-PROPERTIES OF MONOCLONAL-ANTIBODIES TO CORE HISTONES FROM AUTOIMMUNE MICE

Histones are frequent targets of self-reactive antibodies during autoi mmune syndromes. We report the specificities and V region genes of thr ee IgG anti-histone MAbs obtained from autoimmune mice. Each of the MA bs, named LG2-1, LG2-2 and BWA3, is directed against a different deter minant located in the basic amino-terminal domain of core histones LG2 -1 reacts a peptide from histone H3 (residues 30-45), LG2-2 recognizes the amino-terminus of H2B (residues 1-13) and BWA3 binds an epitope c orresponding to a region of high sequence similarity between H2A and H 4 (residues 1-20 and 1-29, respectively). The analysis of their V regi on sequences indicates that the H chain CDRs of these MAbs are remarka ble for the presence of negatively charged amino acid residues that ma y play a role in the binding to cationic histones. The H chain importa nce in conferring reactivity to histones is corroborated by the observ ation that each of the V(H) gene segments of these MAbs is very simila r to V(H) genes of previously described murine anti-histone antibodies .