Selection transduction defect (STD) due to Zap-70 kinase deficiency.
We have previously described a new type of selective T-cell deficiency (STD) characterized by persistent infections reminiscent of severe combined immunodeficiency (SCID). We show here that STD patients carry a mutation of zap-70 resulting in a loss of the activity of this kinase. The thymus of zap-70-/- patients shows the presence of CD4CD8 double positive cells in the cortex, however, only CD4 but not CD8 single positive cells are present in the medulla. Peripheral CD4+ T cells from the zap-70-/- exhibit markedly reduced tyrosine phosphorylation, fail to produce IL-2, and do not proliferate in response to TCR 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 signal transduction and function of single positive CD4 T cells.
Roifman
C M
CM
Division of Immunology/Allergy, Hospital for Sick Children, Toronto, ON, Canada.
D000595:Amino Acid Sequence; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000172:deficiency / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction; D051746:ZAP-70 Protein-Tyrosine Kinase
D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human