title: Restoration of thymopoiesis in pT alpha-/- mice by anti-CD3epsilon antibody treatment or with transgenes encoding activated Lck or tailless pT alpha.
abstract: Mice deficient for the pre-TCR alpha (pT alpha) chain cannot form a pre-T cell receptor (TCR) and exhibit a severe defect in early T cell development, characterized by lack of "beta selection" and impaired generation of double-positive (DP) thymocytes. Here, we demonstrate that intraperitoneal injection of CD3epsilon-specific antibodies into pT alpha-/- x RAG-/- mice or introduction of an activated p56(lck) transgene in pT alpha-/- mice fully restores the number of DP thymocytes, and that expression of a transgenic pT alpha chain lacking its cytoplasmic portion can overcome all developmental defects associated with pT alpha deficiency. These results allow a better definition of the role of pT alpha in pre-TCR signal transduction and provide conclusive evidence that the cytoplasmic tail of pT alpha is not essential for pre-TCR signaling.
authors.affiliation: Basel Institute for Immunology, Switzerland.
authors.forename: H J
authors.initials: HJ
authors.lastname: Fehling
authors.forename: B M
authors.initials: BM
authors.lastname: Iritani
authors.forename: A
authors.initials: A
authors.lastname: Krotkova
authors.forename: K A
authors.initials: KA
authors.lastname: Forbush
authors.forename: C
authors.initials: C
authors.lastname: Laplace
authors.forename: R M
authors.initials: RM
authors.lastname: Perlmutter
authors.forename: H
authors.initials: H
authors.lastname: von Boehmer
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000502:physiology*; D002454:Cell Differentiation; D003593:Cytoplasm; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000235:genetics; D017384:Sequence Deletion; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology; D019076:Transgenes; D019061:src-Family Kinases / Q000502:physiology*
chemical_list: D017252:CD3 Complex; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases