Restoration of T cell development in RAG-2-deficient mice by functional TCR transgenes.
Introduction of TCR alpha transgene, TCR beta transgene, or both into RAG-2-/-mice differentially rescues T cell development. RAG-2-/- mice have small numbers of TCR-CD4-CD8-(double negative, DN) thymocytes that express CD3 gamma delta epsilon and zeta proteins intracellularly. Introduction of a TCR beta transgene, but not a TCR alpha transgene, into the RAG-2-/- background restored normal numbers of thymocytes. These cells were CD4+CD8+ (double positive, DP) and expressed small amounts of surface TCR beta chain dimers in association with CD3 gamma delta epsilon but not zeta. RAG-2-/- mice that expressed alpha and beta TCR transgenes developed both DP and single positive thymocytes. Thus, the TCR beta subunit, possibly in association with a novel CD3 complex, participates in the DN to the DP transition.
Shinkai
Y
Y
Howard Hughes Medical Institute, Children's Hospital, Boston, MA 02115.
Koyasu
S
S
Nakayama
K
K
Murphy
K M
KM
Loh
D Y
DY
Reinherz
E L
EL
Alt
F W
FW
D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D017252:CD3 Complex / Q000032:analysis / Q000235:genetics*; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002462:Cell Membrane / Q000276:immunology; D004268:DNA-Binding Proteins; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D011506:Proteins / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000235:genetics*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D011506:Proteins; C499308:Rag2 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; C064655:V(D)J recombination activating protein 2