Interferon-alpha-induced endogenous superantigen. a model linking environment and autoimmunity.
We earlier proposed that a human endogenous retroviral (HERV) superantigen (SAg) IDDMK(1,2)22 may cause type I diabetes by activating autoreactive T cells. Viral infections and induction of interferon-alpha (IFN-alpha) are tightly associated with the onset of autoimmunity. Here we establish a link between viral infections and IFN-alpha-regulated SAg expression of the polymorphic and defective HERV-K18 provirus. HERV-K18 has three alleles, IDDMK(1,2)22 and two full-length envelope genes, that all encode SAgs. Expression of HERV-K18 SAgs is inducible by IFN-alpha and this is sufficient to stimulate V beta 7 T cells to levels comparable to transfectants constitutively expressing HERV-K18 SAgs. Endogenous SAgs induced via IFN-alpha by viral infections is a novel mechanism through which environmental factors may cause disease in genetically susceptible individuals.
Stauffer
Y
Y
Department of Genetics and Microbiology, University of Geneva Medical School, 1211 Geneva 4, Switzerland.
Marguerat
S
S
Meylan
F
F
Ucla
C
C
Sutkowski
N
N
Huber
B
B
Pelet
T
T
Conrad
B
B
D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D000071178:CD48 Antigen; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000821:virology*; D020077:Endogenous Retroviruses / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004777:Environment; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007962:Leukocytes / Q000821:virology; D008213:Lymphocyte Activation; D008565:Membrane Proteins; D018448:Models, Immunological; D011533:Proviruses / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012367:RNA, Viral / Q000096:biosynthesis; D018089:Superantigens / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D014162:Transfection; D014777:Virus Diseases / Q000150:complications
D015703:Antigens, CD; D000071178:CD48 Antigen; C107453:ERVK-18 protein, human; D015686:Gene Products, env; D016898:Interferon-alpha; D008565:Membrane Proteins; D012367:RNA, Viral; D018089:Superantigens