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

Research output: Contribution to journalArticlepeer-review

Authors

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

Colleges, School and Institutes

External organisations

  • Friedrich-Alexander University Erlangen-Nuremberg

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.

Details

Original languageEnglish
Pages (from-to)303-9
Number of pages7
JournalScandinavian Journal of Immunology
Volume56
Issue number3
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