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 language | English |
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Pages (from-to) | 303-9 |
Number of pages | 7 |
Journal | Scandinavian Journal of Immunology |
Volume | 56 |
Issue number | 3 |
DOIs | |
Publication status | Published - Sept 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