Human severe combined immunodeficiency due to a defect in ZAP-70, a T cell tyrosine kinase

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Science  10 Jun 1994:
Vol. 264, Issue 5165, pp. 1596-1599
DOI: 10.1126/science.8202712


A homozygous mutation in the kinase domain of ZAP-70, a T cell receptor-associated protein tyrosine kinase, produced a distinctive form of human severe combined immunodeficiency. Manifestations of this disorder included profound immunodeficiency, absence of peripheral CD8+ T cells, and abundant peripheral CD4+ T cells that were refractory to T cell receptor-mediated activation. These findings demonstrate that ZAP-70 is essential for human T cell function and suggest that CD4+ and CD8+ T cells depend on different intracellular signaling pathways to support their development or survival.

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