DEVELOPMENTAL ARREST OF NK1.1(+) T-CELL ANTIGEN RECEPTOR (TCR)-ALPHA/BETA(+) T-CELLS AND EXPANSION OF NK1.1(+) TCR-GAMMA/DELTA(+) T-CELL DEVELOPMENT IN CD3-ZETA-DEFICIENT MICE

The relationship between the structure of the T cell antigen receptor (TCR)-CD3 complex and development of NK1.1(+) T cells was investigated. The TCR complex of freshly isolated NK1.1(+) TCR-alpha/beta(+) thymocytes contained CD3 zeta homodimers and CD3 zeta-FcR gamma heterodimers, whereas that of the majority of NK1.1(-) T cells did not contain FcR gamma. The function of CD3 zeta and FcR gamma in the development of NK1.1(+) T cells was determined by analyzing CD3 zeta- and FcR gamma-deficient mice. The NK1.1(+) T cells from wild-type and CD3 zeta-deficient mice had equal levels of CD3 expression. However, the development of NK1.1(+) TCR-alpha/beta(+) T cells was almost completely disrupted in thymus and spleen in CD3 zeta-deficient mice, whereas no alteration was observed in FcR gamma-deficient mice. In contrast, the number of novel NK1.1(+) TCR-gamma/delta(+) thymocytes expressing a surface phenotype similar to NK1.1(+) TCR-alpha/beta(+) thymocytes increased approximately six times in CD3 zeta-deficient mice. These findings establish the distinct roles of the CD3 zeta chain in the development of the following different thymic T cell compartments: NK1.1(-) TCR(+), NK1.1(+) TCR-alpha/beta(+), and NK1.1(+) TCR-gamma/delta(+) thymocytes, which cannot be replaced by CD3 eta or FcR gamma chains.