Essential role for ZAP-70 in both positive and negative selection of thymocytes View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1995-08

AUTHORS

I Negishi, N Motoyama, K Nakayama, K Nakayama, S Senju, S Hatakeyama, Q Zhang, A C Chan, D Y Loh

ABSTRACT

During thymic development, T cells that can recognize foreign antigen in association with self major histocompatibility complex (MHC) are selected for survival (positive selection) and autoreactive T cells are eliminated (negative selection). Both of these selective events are mediated by interaction between the T-cell receptor (TCR) and the peptide-MHC complex. But the signalling pathways that lead to cell survival or to cell death are still unclear. ZAP-70 is a protein tyrosine kinase (PTK) that is associated with the TCR signalling subunits (CD3 and zeta) and is expressed in T cells and natural killer cells. It has been shown that ZAP-70 plays a crucial role in T-cell activation and development. Here we show that mice lacking ZAP-70 had neither CD4 nor CD8 single-positive T cells, but human ZAP-70 reconstituted both CD4 and CD8 single-positive populations. Moreover, ZAP-70-/- thymocytes were not deleted by peptide antigens. Natural killer cell function was intact in the absence of ZAP-70. These data suggest that ZAP-70 is a central signalling molecule during thymic selection for CD4 and CD8 lineage. More... »

PAGES

435-438

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/376435a0

DOI

http://dx.doi.org/10.1038/376435a0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1002096734

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/7630421


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