Format

Send to

Choose Destination
See comment in PubMed Commons below
Immunology. 2014 Apr;141(4):587-95. doi: 10.1111/imm.12220.

A ZAP-70 kinase domain variant prevents thymocyte-positive selection despite signalling CD69 induction.

Author information

1
Department of Immunology, John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia.

Abstract

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.

KEYWORDS:

T cells; genetics; thymic selection

PMID:
24266404
PMCID:
PMC3956432
DOI:
10.1111/imm.12220
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley Icon for PubMed Central
    Loading ...
    Support Center