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-Chain in Patients with Systemic Lupus Erythematosus1
* Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910;
Department of Medicine, Uniformed Services University of Health Sciences, Bethesda, MD 20814; and
Department of Medicine, Washington Hospital Center, Washington, DC, 20005
Systemic lupus erythematosus (SLE), the prototypic autoimmune
disease, is characterized by defective expression of TCR 
-chain.
Elf-1 (E-74-like factor) is a member of the Ets (E-26-specific) family
and is crucial for the basal transcription of TCR -chain in Jurkat
cells. We previously demonstrated that Elf-1 exists in the cytoplasm
mainly as 80-kDa form and after phosphorylation and
O-glycosylation it moves to the nucleus as a 98-kDa
which binds DNA. We now demonstrate that Elf-1 is crucial for the
transactivation of TCR -chain promoter in normal and SLE T cells.
Defective expression of TCR -chain in SLE T cells is associated with
two distinct molecular defects in the generation of the 98-kDa DNA
binding Elf-1 form. In the first, the levels of the 98-kDa form were
either decreased or absent. In the second, the apparent levels of the
nuclear Elf-1 form were normal but included only two of the three bands
into which the nuclear Elf-1 form separated in isoelectric focusing
gels. Because both the transcription and the translation processes of
Elf-1 gene are normal in SLE T cells, our data
demonstrate that abnormal posttranslational mechanisms of the Elf-1
protein result in defective expression of functional Elf-1, and
consequently, the transcriptional defect of TCR -chain in patients
of SLE.
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