Abstract
The majority of regulatory Foxp3+CD4+ T cells naturally arises in the thymus. It has been proposed that T cell receptors (TCRs) on these cells recognize self-MHC class II-peptide complexes with high or higher affinity and that their specificities mirror specificities of autoreactive T cells. Here, we analyzed hundreds of TCRs derived from regulatory or nonregulatory T cells and found little evidence that the former population preferably recognizes self-antigens as agonists. Instead, these cells recognized foreign MHC-peptide complexes as often as nonregulatory T cells. Our results show that high-affinity, autoreactive TCRs are rare on all CD4+ T cells and suggest that selecting self-peptide is different from the peptide that activates the same regulatory T cells in the periphery.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Amino Acid Sequence
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Animals
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Antigen Presentation / immunology
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Autoantigens / immunology*
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Flow Cytometry
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Forkhead Transcription Factors / immunology*
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Histocompatibility Antigens Class II / immunology
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Lymphocyte Activation / immunology
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Mice
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Molecular Sequence Data
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Polymorphism, Single-Stranded Conformational
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology
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Reverse Transcriptase Polymerase Chain Reaction
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Self Tolerance / immunology*
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T-Lymphocyte Subsets / immunology*
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T-Lymphocytes, Regulatory / immunology*
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Wasting Syndrome / immunology
Substances
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Autoantigens
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Histocompatibility Antigens Class II
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Receptors, Antigen, T-Cell