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 language | English (US) |
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Pages (from-to) | 2354-2362 |
Number of pages | 9 |
Journal | European Journal of Immunology |
Volume | 42 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2012 |
Keywords
- Allelic exclusion
- Arthritis
- Autoimmunity
- Dual TCR