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alphabeta T-cell receptors with a central CDR3 cysteine are enriched in CD8alphaalpha intraepithelial lymphocytes and their thymic precursors


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 TCRalphabeta(+) CD8alphaalpha(+) 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 TCRalpha or TCRbeta 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 naive T cells. These findings reveal a TCR-intrinsic motif that distinguishes Type A IELp and IEL from T-reg and naive T cells.

Type Journal
ISBN 1440-1711 (Electronic) 0818-9641 (Linking)
Authors Wirasinha, R. C.; Singh, M.; Archer, S. K.; Chan, A.; Harrison, P. F.; Goodnow, C. C.; Daley, S. R.
Responsible Garvan Author Prof Christopher Goodnow
Published Date 2018-07-01
Published Volume 96
Published Issue 6
Published Pages 553-561
Status Published in-print
DOI 10.1111/imcb.12047
URL link to publisher's version