Incomplete TCR-β allelic exclusion accelerates spontaneous autoimmune arthritis in K/BxN TCR transgenic mice

Jennifer L. Auger, Stefanie Haasken, Elizabeth M. Steinert, Bryce A. Binstadt

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Allelic exclusion of antigen receptor loci is a fundamental mechanism of immunological self-tolerance. Incomplete allelic exclusion leads to dual T-cell receptor (TCR) expression and can allow developing autoreactive αβ T lymphocytes to escape clonal deletion. Because allelic exclusion at the TCR-β locus is more stringent than at the TCR-α locus, dual TCR-β expression has not been considered a likely contributor to autoimmunity. We show here that incomplete TCR-β allelic exclusion permits developing thymocytes bearing the autoreactive, transgene-encoded KRN TCR to be positively selected more efficiently, thereby accelerating the onset of spontaneous autoimmune arthritis. Our findings highlight dual TCR-β expression as a mechanism that can enhance the maturation of autoreactive pathogenic T cells and lead to more rapid development of autoimmune disease.

Original languageEnglish (US)
Pages (from-to)2354-2362
Number of pages9
JournalEuropean Journal of Immunology
Volume42
Issue number9
DOIs
StatePublished - Sep 2012

Keywords

  • Allelic exclusion
  • Arthritis
  • Autoimmunity
  • Dual TCR

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