title: A normal T cell receptor beta CDR3 length distribution in patients with APECED.
abstract: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by mutations in the AIRE gene. Murine studies suggest that AIRE controls thymic expression of tissue-restricted antigens, its absence allowing nonselected autoreactive cells to escape. We tested this in humans using the TCRβ CDR3 length repertoire as a surrogate of thymic selection, as it shortens during the process. Analysis of healthy thymuses showed an altogether 1.9 base pair shortening, starting at the CD4(+)CD8(+)CD3(low) stage and continuing until the CD4(+) subset, likely encompassing both the positive and negative selection. Comparison of five APECED patients with eight healthy controls showed a skewed repertoire with oligoclonal expansions in the patients' CD4(+) and CD8(+) populations. The average CDR3 length, however, was normal and unaffected by the skewing. This was also true of the hypothesized autoreactive CD8(+)CD45RA(+) population. We failed to detect a subset with an abnormally long CDR3 repertoire, as would be predicted by a failure in selection.
authors.affiliation: Haartman Institute, Department of Bacteriology and Immunology, and Research Programs Unit, Immunobiology, University of Helsinki, PB 21, FIN-00014 University of Helsinki, Finland.
authors.forename: Heikki J
authors.initials: HJ
authors.lastname: Niemi
authors.affiliation: Haartman Institute, Department of Bacteriology and Immunology, and Research Programs Unit, Immunobiology, University of Helsinki, PB 21, FIN-00014 University of Helsinki, Finland.
authors.forename: Sini
authors.initials: S
authors.lastname: Laakso
authors.affiliation: Department of Surgery, Hospital for Children and Adolescents, Helsinki University Hospital, PB 281, FIN-00029 HUS, Finland.
authors.forename: Jukka T
authors.initials: JT
authors.lastname: Salminen
authors.affiliation: Haartman Institute, Department of Bacteriology and Immunology, and Research Programs Unit, Immunobiology, University of Helsinki, PB 21, FIN-00014 University of Helsinki, Finland.
authors.forename: T Petteri
authors.initials: TP
authors.lastname: Arstila
authors.affiliation: Haartman Institute, Department of Bacteriology and Immunology, and Research Programs Unit, Immunobiology, University of Helsinki, PB 21, FIN-00014 University of Helsinki, Finland. Electronic address: anni.tuulasvaara@helsinki.fi.
authors.forename: Anni
authors.initials: A
authors.lastname: Tuulasvaara
mesh_terms: D000328:Adult; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics / Q000276:immunology*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012641:Selection, Genetic
chemical_list: D022801:Complementarity Determining Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012313:RNA
keywords: AIRE; APECED; T cell; T cell receptor; Thymus