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PMID: 17869133 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Nonself-antigens are the cognate specificities of Foxp3+ regulatory T cells.

Immunity ·Vol. 27 ·No. 3 ·2007-09-00 ·Pages 493-504

Pacholczyk R, Kern J, Singh N, Iwashima M, Kraj P, Ignatowicz L

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.

MeSH Terms
Adoptive Transfer Amino Acid Sequence Animals Antigen Presentation/immunology Autoantigens/immunology Flow Cytometry Forkhead Transcription Factors/immunology Histocompatibility Antigens Class II/immunology Lymphocyte Activation/immunology Mice Molecular Sequence Data Polymorphism, Single-Stranded Conformational Receptors, Antigen, T-Cell/genetics,immunology Reverse Transcriptase Polymerase Chain Reaction Self Tolerance/immunology T-Lymphocyte Subsets/immunology T-Lymphocytes, Regulatory/immunology Wasting Syndrome/immunology
Chemicals
Autoantigens Forkhead Transcription Factors Foxp3 protein, mouse Histocompatibility Antigens Class II Receptors, Antigen, T-Cell
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Pacholczyk Rafal
Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta, GA 30912, USA. [email protected]
Kern Joanna
Singh Nagendra
Iwashima Makio
Kraj Piotr
Ignatowicz Leszek
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1074-7613
Published
2007-09-00
Pages
493-504
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2276657
Subset
IM
Grants
NCI NIH HHS · R01 CA107349 · United States
NIAID NIH HHS · AI041145-07A1 · United States
NCI NIH HHS · CA107349-01A1 · United States
NIAID NIH HHS · R01 AI041145-09 · United States
NIAID NIH HHS · R01 AI041145 · United States
NIDDK NIH HHS · R01 DK099264 · United States
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