NUCLEOSOME-SPECIFIC ANTIBODY FROM AN AUTOIMMUNE MRL/MP-LPR/LPR MOUSE

Objective. To characterize the binding properties and variable-region sequences of LG4-1, a monoclonal antibody from an autoimmune MRL/Mp-lpr/lpr mouse that reacts specifically with nucleosome core particles and represents a new antinuclear antibody specificity. Methods. The reactivity of the antibody against various nuclear substrates was determined using an enzymatic immunoassay, and the variable-region genes were sequenced from messenger RNA, using the dideoxy chain termination method. Results. LG4-1 was found to react with nucleosome core particles but not with individual histones and DNA, or with various histone-histone and histone-DNA complexes. It was demonstrated that this antibody is encoded by a combination of variable-region genes and gene segments that have undergone few somatic mutations. Conclusion. The nucleosome core particle expresses a unique conformational autoepitope(s) resulting from the ordered association of histones and DNA.