A ribonucleic acid-specific antibody produced during autoimmune disease: evidence for nucleotide sequence specificity.

A hybridoma secreting RNA-binding autoantibody has been produced by fusion of spleen cells from autoimmune NZB/NZWF1 mice with drug-resistant IgG2b-producing myeloma cells from BALB/c mice. Studies on the specificity of the purified monoclonal autoantibody revealed: (a) absolute specificity for ribopolynucleotides as compared with deoxyribopolynucleotides; (b) specificity for single-stranded RNA as compared with double-stranded RNA; (c) high affinity for the random copolymer poly(G, C); and (d) preference for the random heteropolymer poly(G, C, U). These studies were complemented by stoichiometric measurements of the antibody-RNA complex and computer analysis of the abundance of various di-, tri- and tetranucleotide sequences in native RNA. Taken together, these data suggest that the antigenic determinant recognized by the monoclonal autoantibody is largely composed of a trinucleotide sequence of single-stranded RNA containing, G, C and U residues.