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Sci. Signal., 19 July 2011
Vol. 4, Issue 182, p. ra47
[DOI: 10.1126/scisignal.2001765]

RESEARCH ARTICLES

PreTCR and TCR{gamma}{delta} Signal Initiation in Thymocyte Progenitors Does Not Require Domains Implicated in Receptor Oligomerization

Juliet Mahtani-Patching1*, Joana F. Neves1,2*, Dick John Pang1, Kostadin V. Stoenchev1, Ana M. Aguirre-Blanco1, Bruno Silva-Santos3,4, and Daniel J. Pennington1{dagger}

1 Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK.
2 Programa Doutoral de Biologia Experimental e Biomedicina, Centro de Neurociências e Biologia Celular, Universidade de Coimbra, 3000-000 Coimbra, Portugal.
3 Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal.
4 Instituto Gulbenkian de Ciência, 2780-000 Oeiras, Portugal.

* These authors contributed equally to this work.

Abstract: Whether thymocytes adopt an αβ or a {gamma}{delta} 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 {gamma}{delta} 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 TCR{delta}, is a unifying mechanism that initiates signaling in early CD4CD8 double-negative (DN) thymocyte progenitors. Here, we demonstrate that the extracellular regions of pTα and TCR{delta} that are implicated in mediating receptor oligomerization were not required for signal initiation from the preTCR or TCR{gamma}{delta}. Indeed, a truncated TCR{gamma}{delta} 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 {gamma}{delta} T cell fate.

{dagger} To whom correspondence should be addressed. E-mail: d.pennington{at}qmul.ac.uk

Citation: J. Mahtani-Patching, J. F. Neves, D. J. Pang, K. V. Stoenchev, A. M. Aguirre-Blanco, B. Silva-Santos, D. J. Pennington, PreTCR and TCR{gamma}{delta} Signal Initiation in Thymocyte Progenitors Does Not Require Domains Implicated in Receptor Oligomerization. Sci. Signal. 4, ra47 (2011).

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