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Nucleosome-specific antibody from an autoimmune MRL/Mp-lpr/lpr mouse
J A Losman1, T M Fasy, K E Novick
1Garden State Cancer Center, Newark, New Jersey.
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.