title: PreTCR and TCRγδ signal initiation in thymocyte progenitors does not require domains implicated in receptor oligomerization.
abstract: Whether thymocytes adopt an αβ or a γδ T cell fate in the thymus is determined at the β selection checkpoint by the relatively weak or strong signals that are delivered by either the pre-T cell receptor (preTCR) or the γδ TCR, respectively. Signal initiation at the β selection checkpoint is thought to be independent of ligand engagement of these receptors. Some reports have suggested that receptor oligomerization, which is thought to be mediated by either the immunoglobulin (Ig)-like domain of the preTCRα (pTα) chain or the variable domain of TCRδ, is a unifying mechanism that initiates signaling in early CD4(-)CD8(-) double-negative (DN) thymocyte progenitors. Here, we demonstrate that the extracellular regions of pTα and TCRδ that are implicated in mediating receptor oligomerization were not required for signal initiation from the preTCR or TCRγδ. Indeed, a truncated TCRγδ that lacked all of its extracellular Ig-like domains still formed a signaling-competent TCR that drove cells through the β selection checkpoint. These observations suggest that signal initiation in DN thymocytes is simply a consequence of the surface-pairing of TCR chains, with signal strength being a function of the abundances of surface TCRs. Thus, processes that regulate the surface abundances of TCR complexes in DN cells, such as oligomerization-induced endocytosis, would be predicted to have a major influence in determining whether cells adopt an αβ versus γδ T cell fate.
authors.affiliation: 1Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK.
authors.forename: Juliet
authors.initials: J
authors.lastname: Mahtani-Patching
authors.forename: Joana F
authors.initials: JF
authors.lastname: Neves
authors.forename: Dick John
authors.initials: DJ
authors.lastname: Pang
authors.forename: Kostadin V
authors.initials: KV
authors.lastname: Stoenchev
authors.forename: Ana M
authors.initials: AM
authors.lastname: Aguirre-Blanco
authors.forename: Bruno
authors.initials: B
authors.lastname: Silva-Santos
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Pennington
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054503:Lymphoid Progenitor Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D055503:Protein Multimerization / Q000235:genetics / Q000276:immunology*; D017434:Protein Structure, Tertiary; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta