A human autoimmune protein associated with U1 RNA contains a region of homology that is cross-reactive with retroviral p30gag antigen

Cell. 1987 Oct 23;51(2):211-20. doi: 10.1016/0092-8674(87)90148-6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies / immunology
  • Antigens, Viral / immunology*
  • Autoantigens / genetics*
  • Autoantigens / immunology
  • Autoimmune Diseases / blood
  • Base Sequence*
  • Cloning, Molecular
  • Cross Reactions
  • DNA / genetics
  • Genetic Code
  • Humans
  • Immune Sera / immunology
  • Molecular Sequence Data
  • Moloney murine leukemia virus / metabolism
  • Retroviridae / immunology*
  • Ribonucleoproteins / immunology*
  • Ribonucleoproteins, Small Nuclear
  • Sequence Homology, Nucleic Acid*
  • Viral Proteins / genetics

Substances

  • Antibodies
  • Antigens, Viral
  • Autoantigens
  • Immune Sera
  • Ribonucleoproteins
  • Ribonucleoproteins, Small Nuclear
  • Viral Proteins
  • DNA