title: Nonself-antigens are the cognate specificities of Foxp3+ regulatory T cells.
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.
authors.affiliation: Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta, GA 30912, USA. rpacholczyk@mcg.edu
authors.forename: Rafal
authors.initials: R
authors.lastname: Pacholczyk
authors.forename: Joanna
authors.initials: J
authors.lastname: Kern
authors.forename: Nagendra
authors.initials: N
authors.lastname: Singh
authors.forename: Makio
authors.initials: M
authors.lastname: Iwashima
authors.forename: Piotr
authors.initials: P
authors.lastname: Kraj
authors.forename: Leszek
authors.initials: L
authors.lastname: Ignatowicz
mesh_terms: D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D018807:Polymorphism, Single-Stranded Conformational; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017634:Self Tolerance / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D019282:Wasting Syndrome / Q000276:immunology
chemical_list: D001324:Autoantigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell