Apoptosis of the teratocarcinoma cell line Tera-1 leads to the cleavage of HERV-K10gag proteins by caspases and/or granzyme B

T D Beyer, W Kolowos, I E Dumitriu, R E Voll, P Heyder, U S Gaipl, J R Kalden, M Herrmann

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Redistribution, post-translational modifications and coclustering with viral antigens contribute to the immunogenicity of apoptotic cell-derived autoantigens. Almost all known targets of the humoral autoimmune response in systemic lupus erythematosus (SLE) are cleaved by caspases or granzyme B during apoptosis. Antibodies against retroviral proteins can frequently be detected in the sera of SLE patients without overt retroviral infections. These antibodies may represent cross-reactive antibodies or may have been induced by proteins encoded by endogenous retroviral sequences. We used Tera-1 cells that abundantly express a group-specific antigen of human endogenous retroviruses, HERV-K10gag polyprotein, to investigate its processing during apoptosis. Tera-1 cells induced to undergo apoptosis showed an altered HERV-K10gag processing compared with viable cells. In addition, granzyme B was able to cleave HERV-K10gag isolated from viable Tera-1 cells. Similar to nuclear autoantigens, endogenous retroviral proteins are cleaved during the execution phase of apoptosis. These post-translational modifications may result in the generation of T-cell neoepitopes or a changed epitope hierarchy of retroviral proteins. Therefore, immunogenicity of retroviral antigens in SLE patients may result from a similar mechanism as described for nuclear autoantigens.

Original languageEnglish
Pages (from-to)303-9
Number of pages7
JournalScandinavian Journal of Immunology
Volume56
Issue number3
DOIs
Publication statusPublished - Sep 2002

Keywords

  • Amino Acid Sequence
  • Antibodies, Viral/blood
  • Apoptosis
  • Caspase Inhibitors
  • Caspases/metabolism
  • Cell Extracts/analysis
  • Cysteine Proteinase Inhibitors/pharmacology
  • Endogenous Retroviruses
  • Gene Products, gag/chemistry
  • Granzymes
  • Humans
  • Immunoblotting
  • Lupus Erythematosus, Systemic/immunology
  • Serine Endopeptidases/metabolism
  • Teratocarcinoma/enzymology
  • Tumor Cells, Cultured
  • Viral Proteins

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