A human autoimmune protein associated with U1 RNA contains a region of homology that is cross-reactive with retroviral p30gag antigen.
cDNA encoding a 70 kd protein (70K) associated with U1 small nuclear ribonucleoprotein (snRNP) was cloned from a human brain-stem library using autoantibodies from patients with connective tissue disease. The cDNA-derived amino acid sequence contains 23 residues homologous to a region of murine leukemia virus group-specific antigen p30gag. The homology residues in an antigenic portion of the 70K protein and is defined by a core consensus sequence, ETPEEREERRR, that occurs as a tandem repeat in p30gag of most mammalian type C retroviruses. Anti-p30gag antibodies recognized a recombinant 70K-LacZ fusion protein as well as U1 snRNPs. Using synthetic peptides as competitors, we demonstrated that the region of homology encompasses the site of immunological cross-reactivity. Thus autoantibodies against U1 snRNPs were elicited by immunization with p30gag. On the basis of these findings, we suggest a role for retroviruses in the initiation of autoimmunity.
D000906:Antibodies / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D001324:Autoantigens / Q000235:genetics* / Q000276:immunology; D001327:Autoimmune Diseases / Q000097:blood; D001483:Base Sequence; D003001:Cloning, Molecular; D003429:Cross Reactions; D004247:DNA / Q000235:genetics; D005815:Genetic Code; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000378:metabolism; D012190:Retroviridae / Q000276:immunology*; D012261:Ribonucleoproteins / Q000276:immunology*; D017411:Ribonucleoproteins, Small Nuclear; D012689:Sequence Homology, Nucleic Acid; D014764:Viral Proteins / Q000235:genetics
D000906:Antibodies; D000956:Antigens, Viral; D001324:Autoantigens; D007106:Immune Sera; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; D014764:Viral Proteins; D004247:DNA