title: A mutation in zap-70 protein tyrosine kinase results in a selective immunodeficiency.
abstract: We have previously described a new type of selective T-cell deficiency characterized by persistent infections reminiscent of severe combined immunodeficiency. We show here that selective T-cell deficiency patients carry a mutation of zap-70 protein tyrosine kinase, resulting in a loss of the activity of this kinase. The thymus of zap-70(-1-1) patients shows the presence of CD4CD8 double-positive cells in the cortex, however, only CD4, and not CD8, single-positive cells are present in the medulla. Peripheral CD4+ T cells from the zap-70(-1-1) patients exhibit markedly reduced tyrosine phosphorylation, fail to produce interleukin-2, and do not proliferate in response to T-cell receptor stimulation by mitogens or antigens. Thus zap-70 kinase appears to be indispensable for the development of CD8 single-positive T cells as well as for the signal transduction and function of single-positive CD4 T cells.
authors.affiliation: Division of Immunology/Allergy, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: C M
authors.initials: CM
authors.lastname: Roifman
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002454:Cell Differentiation; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000201:enzymology / Q000235:genetics*; D007223:Infant; D008969:Molecular Sequence Data; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics*; D011948:Receptors, Antigen, T-Cell / Q000172:deficiency*; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D051746:ZAP-70 Protein-Tyrosine Kinase
chemical_list: D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human