Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antigens, CD / biosynthesis
-
Antigens, CD / genetics
-
Autoimmunity*
-
CD4-Positive T-Lymphocytes / immunology
-
CD48 Antigen
-
Cells, Cultured
-
Diabetes Mellitus, Type 1 / virology*
-
Endogenous Retroviruses / genetics
-
Endogenous Retroviruses / immunology*
-
Endogenous Retroviruses / metabolism
-
Environment
-
Gene Products, env / genetics
-
Gene Products, env / immunology
-
Humans
-
Interferon-alpha / pharmacology*
-
Leukocytes / virology
-
Lymphocyte Activation
-
Membrane Proteins
-
Models, Immunological*
-
Proviruses / genetics
-
Proviruses / immunology
-
Proviruses / metabolism
-
RNA, Viral / biosynthesis
-
Superantigens / biosynthesis
-
Superantigens / genetics*
-
Superantigens / immunology
-
Transfection
-
Virus Diseases / complications
Substances
-
Antigens, CD
-
CD48 Antigen
-
ERVK-18 protein, human
-
Gene Products, env
-
Interferon-alpha
-
Membrane Proteins
-
RNA, Viral
-
Superantigens