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PMID:7630421
| Citation |
Negishi, I, Motoyama, N, Nakayama, K, Nakayama, K, Senju, S, Hatakeyama, S, Zhang, Q, Chan, AC and Loh, DY (1995) Essential role for ZAP-70 in both positive and negative selection of thymocytes. Nature 376:435-8 |
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| 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. |
| Links |
PubMed Online version:10.1038/376435a0 |
| Keywords |
Animals; CD4-Positive T-Lymphocytes/cytology; CD4-Positive T-Lymphocytes/immunology; CD8-Positive T-Lymphocytes/cytology; CD8-Positive T-Lymphocytes/immunology; Cell Differentiation/physiology; Cell Line; Cells, Cultured; Female; Gene Deletion; Humans; Killer Cells, Natural/immunology; Male; Mice; Mice, Inbred C57BL; Protein-Tyrosine Kinases/genetics; Protein-Tyrosine Kinases/physiology; Receptors, Antigen, T-Cell/genetics; Receptors, Antigen, T-Cell/physiology; Severe Combined Immunodeficiency/immunology; Spleen/cytology; Spleen/immunology; Thymus Gland/cytology; Thymus Gland/immunology; Tumor Cells, Cultured; ZAP-70 Protein-Tyrosine Kinase |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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