Document 0277
 DOCN  M95B0277
 TI    Essential role for ZAP-70 in both positive and negative selection of
       thymocytes.
 DT    9511
 AU    Negishi I; Motoyama N; Nakayama K; Nakayama K; Senju S; Hatakeyama S;
       Zhang Q; Chan AC; Loh DY; Howard Hughes Medical Institute, Department of
       Medicine,; Washington University School of Medicine, St Louis, Missouri;
       63110, USA.
 SO    Nature. 1995 Aug 3;376(6539):435-8. Unique Identifier : AIDSLINE
       MED/95356836
 AB    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.
 DE    Animal  Cell Differentiation/PHYSIOLOGY  Cell Line  Cells, Cultured
       CD4-Positive T-Lymphocytes/*CYTOLOGY/IMMUNOLOGY  CD8-Positive
       T-Lymphocytes/*CYTOLOGY/IMMUNOLOGY  Female  Gene Deletion  Human  Killer
       Cells, Natural/IMMUNOLOGY  Male  Mice  Mice, Inbred C57BL
       Protein-Tyrosine Kinase/GENETICS/*PHYSIOLOGY  Receptors, Antigen,
       T-Cell/GENETICS/*PHYSIOLOGY  Severe Combined Immunodeficiency/IMMUNOLOGY
       Spleen/CYTOLOGY/IMMUNOLOGY  Support, Non-U.S. Gov't  Thymus
       Gland/*CYTOLOGY/IMMUNOLOGY  Tumor Cells, Cultured  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).