A normal T cell receptor beta CDR3 length distribution in patients with APECED

Cell Immunol. 2015 Jun;295(2):99-104. doi: 10.1016/j.cellimm.2015.03.005. Epub 2015 Mar 23.

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.

Keywords: AIRE; APECED; T cell; T cell receptor; Thymus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Complementarity Determining Regions / genetics
  • Complementarity Determining Regions / immunology*
  • Female
  • Flow Cytometry
  • Humans
  • Leukocytes, Mononuclear / immunology
  • Male
  • Middle Aged
  • Polyendocrinopathies, Autoimmune / genetics
  • Polyendocrinopathies, Autoimmune / immunology*
  • RNA / chemistry
  • RNA / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Selection, Genetic

Substances

  • Complementarity Determining Regions
  • Receptors, Antigen, T-Cell, alpha-beta
  • RNA

Supplementary concepts

  • Autoimmune polyendocrinopathy syndrome, type 1