Projects per year
Abstract
The thymus plays a crucial role in immune tolerance by exposing developing T cells (thymocytes) to a myriad of self-antigens. Strong T-cell receptor (TCR) engagement induces tolerance in self-reactive thymocytes by stimulating apoptosis or selection into specialized T-cell lineages, including intestinal TCRαβ+ CD8αα+ intraepithelial lymphocytes (IEL). TCR-intrinsic amino acid motifs that can be used to predict whether a TCR will be strongly self-reactive remain elusive. Here, a novel TCR sequence alignment approach revealed that T-cell lineages in C57BL/6 mice had divergent usage of cysteine within two positions of the amino acid at the apex of the complementarity-determining region 3 (CDR3) of the TCRα or TCRβ chain. Compared to pre-selection thymocytes, central CDR3 cysteine usage was increased in IEL and Type A IEL precursors (IELp) and markedly decreased in Foxp3+ regulatory T cells (T-reg) and naïve T cells. These findings reveal a TCR-intrinsic motif that distinguishes Type A IELp and IEL from T-reg and naïve T cells.
Original language | English |
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Pages (from-to) | 553-561 |
Number of pages | 9 |
Journal | Immunology and Cell Biology |
Volume | 96 |
Issue number | 6 |
DOIs | |
Publication status | Published - Jul 2018 |
Keywords
- Central tolerance
- T cells
- T-cell receptor
- Thymus
- VDJ recombination
Projects
- 1 Finished
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Molecular and Cellular basis of inflammatory and immunodeficiency diseases
Mackay, C., Brink, R., Cook, M., Goodnow, C., Mackay-Fisson, F., Sprent, J., Tangye, S. & Vinuesa, C. G.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/12 → 31/12/16
Project: Research
Equipment
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Animal Research Platform (MARP)
Christine Findlay (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility
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Bioinformatics Platform
Deanna Deveson (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility