CD3 epsilon and CD3 zeta cytoplasmic domains can independently generate signals for T cell development and function.
To determine whether CD3 epsilon and CD3 zeta proteins have unique roles in TCR-dependent functions, chimeric genes encoding the extracellular and transmembrane domains of the human IL-2 receptor alpha chain (Tac) fused to a cytoplasmic domain of either the CD3 epsilon or CD3 zeta chain were introduced as transgenes into both normal and RAG2-deficient (RAG2-/-) mice. Developmental arrest of T lineage cells at the CD4, CD8 double-negative stage in the transgenic RAG2-/- thymus was released to the CD4, CD8 double-positive (DP) stage by in vivo cross-linking of TT epsilon or TT zeta with anti-Tac antibody. In TT epsilon + or TT zeta +, RAG2-/- mice, in vitro cross-linking of TT epsilon and TT zeta induced DP thymocyte cell death and proliferation of mature single-positive T cells. Overall, no qualitative differences were observed between TT epsilon- and TT zeta-mediated functions, suggesting that different CD3 components deliver qualitatively similar signals in inducing TCR-dependent functions.
Shinkai
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Y
Howard Hughes Medical Institute, Department of Genetics, Children's Hospital, Boston, Massachusetts, USA.
Ma
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Cheng
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D000818:Animals; D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death; D002454:Cell Differentiation; D003001:Cloning, Molecular; D051379:Mice; D008822:Mice, Transgenic; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D015290:Second Messenger Systems; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology*
D017252:CD3 Complex; D018160:Receptors, Cytoplasmic and Nuclear; D015375:Receptors, Interleukin-2