Isolation and characterization of cDNA encoding the antigenic protein of the human tRNP(Ser)Sec complex recognized by autoantibodies from patients withtype-1 autoimmune hepatitis

Clin Exp Immunol. 2000 Aug;121(2):364-74. doi: 10.1046/j.1365-2249.2000.01280.x.


We previously described autoantibodies against a UGA serine tRNA-protein complex (tRNP(Ser)Sec) in patients with type-1 autoimmune hepatitis [1] and now define the specificity and frequency of this autoantibody and the DNA sequence encoding the tRNA(Ser)Sec-associated antigenic protein. The presence of anti-tRNP(Ser)Sec antibodies was highly specific for type-1 autoimmune hepatitis, as 47.5% of patients were positive compared with none of the control subjects. To characterize the antigenic protein(s), we immunoscreened a human cDNA library with anti-tRNP(Ser)Sec-positive sera. Two clones (19 and 13) were isolated. Clone 19 encodes a protein with a predicted molecular mass of 48.8 kD. Clone 13 is a shorter cDNA, almost identical to clone 19, which encodes a 35.9-kD protein. Expression of both cDNAs was accomplished in Escherichia coli as His-tagged recombinant proteins. Antibodies eluted from both purified recombinant proteins were able to immunoprecipitate the tRNA(Ser)Sec from a HeLa S3 cell extract, demonstrating their cross-reactivity with the mammalian antigenic complex. Recent cloning data relating to the target antigen(s) of autoantibodies in autoimmune hepatitis patients that react with a soluble liver antigen (SLA) and a liver-pancreas antigen (LP) have revealed that these two autoantibodies are identical and that the cloned antigen shows 99% amino acid sequence homology with tRNP(Ser)Sec.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amino Acid Sequence
  • Antibody Specificity
  • Autoantibodies / immunology*
  • Autoantigens / genetics*
  • Autoantigens / immunology
  • Autoimmune Diseases / immunology*
  • Base Sequence
  • Blotting, Western
  • DNA, Complementary / genetics*
  • DNA, Complementary / isolation & purification
  • Genes
  • Genes, Suppressor
  • HeLa Cells / chemistry
  • Hepatitis, Autoimmune / immunology*
  • Humans
  • Liver / immunology
  • Liver Diseases / immunology
  • Macromolecular Substances
  • Middle Aged
  • Molecular Sequence Data
  • Pancreas / immunology
  • RNA, Messenger / genetics*
  • RNA, Transfer, Amino Acyl / metabolism*
  • Recombinant Fusion Proteins / immunology
  • Sensitivity and Specificity


  • Autoantibodies
  • Autoantigens
  • DNA, Complementary
  • Macromolecular Substances
  • RNA, Messenger
  • RNA, Transfer, Amino Acyl
  • Recombinant Fusion Proteins
  • selenocysteinyl-tRNA