Purpose of review: The molecular characterization of inherited T-cell immunodeficiencies has contributed to delineating key factors in human T-cell development. This review reports on the recent description of deleterious mutations in the genes encoding CD3 subunits expressed at the T-lymphocyte membrane in association with the T-cell receptor.
Recent findings: Homozygous mutations in CD3D and CD3E genes lead to a complete block in T-cell development and thus to an early-onset severe combined immunodeficiency phenotype. Thymic studies have shown that the defect in T-cell development occurs at the transition between 'double-negative' and 'double-positive' thymocytes. These results contrast with the partial T-cell immunodeficiency caused by a deficiency in CD3G.
Summary: Two new severe combined immunodeficiency conditions have been reported as a consequence of either CD3D or CD3E deficiency. The distinct phenotype of CD3G deficiency sheds light on the differential roles of CD3 subunits in T-lymphocyte development.