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.
|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|
|Publisher Name||IMMUNOLOGY AND CELL BIOLOGY|
|URL link to publisher's version||https://www.ncbi.nlm.nih.gov/pubmed/29726044|