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LKM-1 autoantibodies recognize a short linear sequence in P450IID6, a cytochrome-P-450 monooxygenase

Academic Article
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Overview

authors

  • Manns, M. P.
  • Griffin, K. J.
  • Sullivan, K. F.
  • Johnson, Eric

publication date

  • October 1991

journal

  • Journal of Clinical Investigation  Journal

abstract

  • LKM-1 autoantibodies, which are associated with autoimmune chronic active hepatitis, recognize P450IID6, a cytochrome P-450 monooxygenase. The reactivities of 26 LKM-1 antisera were tested with a panel of deletion mutants of P450IID6 expressed in Escherichia coli. 22 sera recognize a 33-amino acid segment of P450IID6, and 11 of these recognize a shorter segment, DPAQPPRD. PAQPPR is also found in IE175 of herpes simplex virus type 1 (HSV-1). Antibodies for HSV-1 proteins were detected by ELISA in 17 of 20 LKM-1 sera tested. An immobilized, synthetic peptide, DPAQPPRDC, was used to purify LKM-1 antibodies. Affinity purified LKM-1 autoantibodies react on immunoblots with a protein in BHK cells after infection with HSV-1. 11 of 24 LKM-1 sera, including 3 that recognize DPAQPPRD, also exhibit antibodies to the hepatitis C virus (HCV) protein, C100-3. Affinity purified LKM-1 antibodies did not recognize C100-3. However, partial sequence identity was evident between portions of the immunopositive 33-amino acid segment of P450IID6 and other portions of the putative HCV polyprotein. Immune cross-recognition of P450IID6 and HCV or HSV-1 proteins may contribute to the occurrence of LKM-1 autoantibodies.

subject areas

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Antibodies, Viral
  • Autoantibodies
  • Autoimmune Diseases
  • Cytochrome P-450 Enzyme System
  • Epitopes
  • Female
  • Hepacivirus
  • Hepatitis, Chronic
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Oxygenases
  • Simplexvirus
  • Viral Proteins
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Research

keywords

  • AUTOIMMUNE CHRONIC ACTIVE HEPATITIS
  • EPITOPE MAPPING
  • HEPATITIS-C VIRUS
  • HERPES SIMPLEX VIRUS, TYPE-1
  • IMMUNE CROSS-RECOGNITION
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Identity

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/jci115443

PubMed ID

  • 1717511
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Additional Document Info

start page

  • 1370

end page

  • 1378

volume

  • 88

issue

  • 4

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