Variable region genes of anti-histone autoantibodies from a MRL/Mp-lpr/lpr mouse.

The variable region nucleotide sequences of seven (five IgM and two IgG) anti-histone monoclonal antibodies from a single MRL/Mp-lpr/lpr mouse have been determined. These antibodies are not clonally related and used diverse V, D and J genes. However, six of the seven antibodies have VH segments encoded by genes from the J558 family, two of these (an IgM and an IgG) share an identical VH gene. The isoelectric points of MRA3 and MRA12, the two IgG antibodies of the panel, range from 6.3 to 7.0 and from 6.0 to 6.3, respectively. The second conplementarity-determining region (CDR) of the VH gene of MRA12 (the most acidic and the most strongly histone-reactive antibody) includes only two positively charged but five negatively charged amino acid residues. This feature is unusual since the equivalent CDR in most VHJ558 genes are not comprised predominantly of acidic residues and suggests that such negatively charged residues are important for antibody binding to histones.