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

Nature volume 376, pages 435–438 (1995)Cite this article

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 autoreac-tive 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 complex1. 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 ζ) and is expressed in T cells and natural killer cells2. It has been shown that ZAP-70 plays a crucial role in T-cell activation2–5 and development6–8. Here we show that mice lacking ZAP-70 had neither CD4 nor CDS single-positive T cells, but human ZAP-70 reconstituted both CD4 and CDS single-positive populations. Moreover, ZAP–/– 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.

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Author notes

  1. Andrew C. Chan

    Present address: Department of Biology, Nippon Roche Research Center, 200 Kajiwara, Kamakura Kanagawa, 247, Japan

Authors and Affiliations

  1. Howard Hughes Medical Institute, Departments of Medicine, Genetics and Molecular Microbiology,

    Izumi Negishi, Noboru Motoyama, Kei-ichi Nakayama, Keiko Nakayama, Satoru Senju, Shigetsugu Hatakeyama, Qing Zhang, Andrew C. Chan & Dennis Y. Loh

  2. Division of Rheumatology, Departments of Medicine and Pathology, Washington University School of Medicine, St Louis, Missouri, 63110, USA

    Izumi Negishi, Kei-ichi Nakayama, Keiko Nakayama & Dennis Y. Loh

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Negishi, I., Motoyama, N., Nakayama, Ki. et al. Essential role for ZAP-70 in both positive and negative selection of thymocytes. Nature 376, 435–438 (1995). https://doi.org/10.1038/376435a0

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