Apoptosis of the teratocarcinoma cell line Tera-1 leads to the cleavage of HERV-K10gag proteins by caspases and/or granzyme B.
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.
Institute of Clinical Immunology and Rheumatology, Department of Internal Medicine III, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
T  D
T
Beyer
W
W
Kolowos
I E
IE
Dumitriu
R E
RE
Voll
P
P
Heyder
U S
US
Gaipl
J R
JR
Kalden
M
M
Herrmann
D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000097:blood; D017209:Apoptosis; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002457:Cell Extracts / Q000032:analysis; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D020077:Endogenous Retroviruses; D015683:Gene Products, gag / Q000737:chemistry / Q000378:metabolism*; D053804:Granzymes; D006801:Humans; D015151:Immunoblotting; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D012697:Serine Endopeptidases / Q000378:metabolism*; D018243:Teratocarcinoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D014764:Viral Proteins
D000914:Antibodies, Viral; D061945:Caspase Inhibitors; D002457:Cell Extracts; D015853:Cysteine Proteinase Inhibitors; D015683:Gene Products, gag; C465545:HERV-K10gag protein, K10 retrovirus; D014764:Viral Proteins; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; D020169:Caspases