αβ T-cell receptors with a central CDR3 cysteine are enriched in CD8αα intraepithelial lymphocytes and their thymic precursors

Rushika C. Wirasinha, Mandeep Singh, Stuart K. Archer, Anna Chan, Paul F. Harrison, Christopher C. Goodnow, Stephen R. Daley

Research output: Contribution to journalArticleResearchpeer-review

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 languageEnglish
Pages (from-to)553-561
Number of pages9
JournalImmunology and Cell Biology
Volume96
Issue number6
DOIs
Publication statusPublished - Jul 2018

Keywords

  • Central tolerance
  • T cells
  • T-cell receptor
  • Thymus
  • VDJ recombination

Cite this

Wirasinha, Rushika C. ; Singh, Mandeep ; Archer, Stuart K. ; Chan, Anna ; Harrison, Paul F. ; Goodnow, Christopher C. ; Daley, Stephen R. / αβ T-cell receptors with a central CDR3 cysteine are enriched in CD8αα intraepithelial lymphocytes and their thymic precursors. In: Immunology and Cell Biology. 2018 ; Vol. 96, No. 6. pp. 553-561.
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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 na{\"i}ve T cells. These findings reveal a TCR-intrinsic motif that distinguishes Type A IELp and IEL from T-reg and na{\"i}ve T cells.",
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αβ T-cell receptors with a central CDR3 cysteine are enriched in CD8αα intraepithelial lymphocytes and their thymic precursors. / Wirasinha, Rushika C.; Singh, Mandeep; Archer, Stuart K.; Chan, Anna; Harrison, Paul F.; Goodnow, Christopher C.; Daley, Stephen R.

In: Immunology and Cell Biology, Vol. 96, No. 6, 07.2018, p. 553-561.

Research output: Contribution to journalArticleResearchpeer-review

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