Domains of the TCR beta-chain required for early thymocyte development.
The T cell receptor beta (TCR beta) chain controls the developmental transition from CD4-CD8- to CD4+8+thymocytes. We show that the extracellular constant region and the transmembrane region, but not the variable domain or cytoplasmic tail of the TCR beta chain are required for this differentiation step. TCR beta mutant chains lacking the cytoplasmic tail can be found at the cell surface both in functional TCR/CD3 complexes and in a GPI-anchored monomeric form indicating that the cytoplasmic tail of the TCR beta chain functions as an ER retention signal. The concordance between cell surface expression of the mutant chains as TCR/CD3 complexes and their capacity to mediate thymocyte differentiation supports the CD3 mediated feedback model in which preTCR/CD3 complexes control the developmental transition from CD4-CD8- to CD4+CD8+thymocytes.
Jacobs
H
H
Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Iacomini
J
J
van de Ven
M
M
Tonegawa
S
S
Berns
A
A
D000818:Animals; D017252:CD3 Complex / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002451:Cell Compartmentation; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D004252:DNA Mutational Analysis; D004721:Endoplasmic Reticulum / Q000378:metabolism; D017261:Glycosylphosphatidylinositols; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D011487:Protein Conformation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D019076:Transgenes
D017252:CD3 Complex; D017261:Glycosylphosphatidylinositols; D016693:Receptors, Antigen, T-Cell, alpha-beta