Immunoreactivity between a monoclonal lupus autoantibody and the arginine/aspartic acid repeats within the U1-snRNP 70K autoantigen is conformationally restricted.
Immunoreactivity of the arginine/aspartic acid (RD) repeats of the 70K protein of U1 small nuclear ribonucleoprotein (snRNP) was determined to be conformationally dependent. The monoclonal autoantibody 2.73, isolated from a lupus-prone MRL/n mouse model, is reactive with the RD repeat regions of U1 snRNP 70K protein. Immunochemical analysis of the antigenic determinants with use of chemically synthesized peptides characterized the 2.73 epitope as the RD repeat [Pelsue, S., et al. (1993) Autoimmunity, 15, 231-236] Analysis by circular dichroism (CD) and nuclear magnetic resonance spectroscopy indicates conformational preferences in the immunoreactive peptides. Computer analyses of CD spectra obtained on the RD-containing peptides predict beta-turns and beta-sheet to be the preferred conformations of the RD repeats. This structure was also predicted by the Chou-Fasman algorithm. The RD repeat is believed to be a conserved structural motif; however, the biological function is still unclear. Immunological and biochemical analysis of autoimmune antibodies and their respective antigenic determinants has helped to characterize the possible mechanisms that lead to autoimmune diseases. This is the first report of a conformationally dependent, linear epitope of an autoantibody.
Pelsue
S
S
Department of Biochemistry, North Carolina State University, Raleigh 27695-7622.
Agris
P F
PF
D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000378:metabolism; D001120:Arginine; D001224:Aspartic Acid; D001324:Autoantigens / Q000737:chemistry* / Q000378:metabolism; D002942:Circular Dichroism; D003198:Computer Simulation; D017124:Conserved Sequence; D000939:Epitopes / Q000032:analysis; D006801:Humans; D007118:Immunoassay; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011817:Rabbits; D012091:Repetitive Sequences, Nucleic Acid; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013950:Thymus Gland
D000911:Antibodies, Monoclonal; D001324:Autoantigens; D000939:Epitopes; D010455:Peptides; D017412:Ribonucleoprotein, U1 Small Nuclear; D001224:Aspartic Acid; D001120:Arginine