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.

journal_name

Cell Immunol

journal_title

Cellular immunology

authors

Niemi HJ,Laakso S,Salminen JT,Arstila TP,Tuulasvaara A

doi

10.1016/j.cellimm.2015.03.005

subject

Has Abstract

pub_date

2015-06-01 00:00:00

pages

99-104

issue

2

eissn

0008-8749

issn

1090-2163

pii

S0008-8749(15)00073-8

journal_volume

295

pub_type

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