| First Author | Siggs OM | Year | 2014 |
| Journal | Immunology | Volume | 141 |
| Issue | 4 | Pages | 587-95 |
| PubMed ID | 24266404 | Mgi Jnum | J:211840 |
| Mgi Id | MGI:5576459 | Doi | 10.1111/imm.12220 |
| Citation | Siggs OM, et al. (2014) A ZAP-70 kinase domain variant prevents thymocyte-positive selection despite signalling CD69 induction. Immunology 141(4):587-95 |
| abstractText | Quantitative reductions in T-cell receptor (TCR) signalling are associated with severe immunodeficiency, yet in certain cases can lead to autoimmunity. Mutation of the tyrosine kinase ZAP-70 can cause either of these outcomes, yet the limits of its signal transducing capacity are not well defined. To investigate these limits we have made use of mrtless: a chemically induced mutation of Zap70 associated with T-cell deficiency. Unlike cells devoid of ZAP-70, mrtless thymocytes showed partial induction of CD5 and CD69, and were sensitive to TCR stimulation with a dose-response shifted approximately 10-fold. However, essentially no T cells were able to compensate for the mrtless mutation and mature beyond the CD4(+) CD8(+) stage. This outcome contrasts with a ZAP-70 Src Homology 2 domain mutant strain, where high-affinity self-reactive TCR are positively selected rather than deleted. We discuss these data with respect to current models of TCR signalling in thymocyte selection. |
