Abstract
T cell receptor engagement in the absence of proper accessory signals leads to T cell anergy. E3 ligases are involved in maintaining the anergic state. However, the specific molecules responsible for the induction of anergy have yet to be elucidated. Using microarray analysis we have identified here early growth response gene 2 (Egr-2) and Egr-3 as key negative regulators of T cell activation. Overexpression of Egr2 and Egr3 was associated with an increase in the E3 ubiquitin ligase Cbl-b and inhibition of T cell activation. Conversely, T cells from Egr3(-/-) mice had lower expression of Cbl-b and were resistant to in vivo peptide-induced tolerance. These data support the idea that Egr-2 and Egr-3 are involved in promoting a T cell receptor-induced negative regulatory genetic program.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing / metabolism
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Animals
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Cells, Cultured
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Clonal Anergy / immunology
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Early Growth Response Protein 2
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Early Growth Response Protein 3
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Gene Expression
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Lymphocyte Activation* / immunology
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Mice
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Mice, Knockout
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Mutation / genetics
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Oligonucleotide Array Sequence Analysis
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Proto-Oncogene Proteins c-cbl
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology*
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Transcription Factors / deficiency
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Ubiquitin-Protein Ligases / metabolism
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Up-Regulation
Substances
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Adaptor Proteins, Signal Transducing
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Cblb protein, mouse
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DNA-Binding Proteins
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Early Growth Response Protein 2
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Egr2 protein, mouse
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Egr3 protein, mouse
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Transcription Factors
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Early Growth Response Protein 3
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Proto-Oncogene Proteins c-cbl
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Ubiquitin-Protein Ligases