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 CD 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.
Arase
H
H
Division of Molecular Genetics, Chiba University School of Medicine, Japan.
Ono
S
S
Arase
N
N
Park
S Y
SY
Wakizaka
K
K
Watanabe
H
H
Ohno
H
H
Saito
T
T
D000818:Animals; D000941:Antigens / Q000032:analysis*; D000950:Antigens, Ly; D000954:Antigens, Surface; D017252:CD3 Complex / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D046911:Macromolecular Substances; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins / Q000032:analysis*; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology*; D017452:Receptors, IgG / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology
D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D017252:CD3 Complex; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D046911:Macromolecular Substances; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D017452:Receptors, IgG