A normal T cell receptor beta CDR3 length distribution in patients with APECED
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1
University of Helsinki, Haartman Institute, Department of Bacteriology and Immunology, Finland
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a monogenic autoimmune disease caused by mutations in the AIRE gene. AIRE is thought to control the ectopic expression of tissue specific antigens in the thymus. This would lead to generation of autoreactive T cells in APECED patients. Alternative models suggest that AIRE deficiency might lead to more profound changes in thymic architecture or premature activation of T cells in the thymus. Our objective was to assess these possibilities using TCR CDR3β length repertoire analysis. The repertoire is known to shorten during normal thymic development and therefore a comparison between patients and healthy controls should reveal the existence of a profound developmental defect.
TCR repertoire spectratyping and sequencing were used to calculate average CDR3β lengths of thymocytes and peripheral blood T cell populations.
To analyse the normal thymic shortening further, we examined CDR3β repertoires of DP CD3low, DP CD3high and CD4 SP thymocytes. Significant shortening was observed between each stage, demonstrating coupling of the shortening to positive and negative selection processes. We then proceeded to compare the CDR3β repertoires of CD4+ and CD8+ T cells of patients and controls and their CD45RA and CD45RO subsets, which represent activated and resting or memory cells, respectively. In each case we observed no significant difference in the length repertoires.
Our results suggest that the defect in T cell development in APECED patients is more likely a subtle one, not affecting the overall CDR3β length repertoire of peripheral T cell populations.
Keywords:
APECED,
Autoimmunity,
APS-1,
AIRE,
Thymus
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Niemi
HJ,
Koivula
T,
Salonen
SM,
Arstila
P and
Tuulasvaara
A
(2013). A normal T cell receptor beta CDR3 length distribution in patients with APECED.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00872
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Received:
25 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Mr. Heikki J Niemi, University of Helsinki, Haartman Institute, Department of Bacteriology and Immunology, Helsinki, Finland, heikki.niemi@helsinki.fi