Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Science 8 May 1998:
Vol. 280. no. 5365, pp. 905 - 908
DOI: 10.1126/science.280.5365.905

Reports

Thymocyte Development in the Absence of Pre-T Cell Receptor Extracellular Immunoglobulin Domains

Bryan A. Irving, Frederick W. Alt, Nigel Killeen *

Immature thymocytes express a pre-T cell receptor (pre-TCR) composed of the TCRbeta chain paired with pre-Talpha . Signals from this receptor are essential for passage of thymocytes through a key developmental checkpoint in the thymus. These signals were efficiently delivered in vivo by a truncated form of the murine pre-TCR that lacked all of its extracellular immunoglobulin domains. De novo expression of the truncated pre-TCR or an intact alpha beta TCR was sufficient to activate characteristic TCR signaling pathways in a T cell line. These findings support the view that recognition of an extracellular ligand is not required for pre-TCR function.

B. A. Irving and N. Killeen, Department of Microbiology and Immunology, University of California, San Francisco, CA 94143-0414, USA.
F. W. Alt, Howard Hughes Medical Institute and Department of Genetics and Pediatrics, Children's Hospital and Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA.
*   To whom correspondence should be addressed. E-mail: nigel{at}itsa.ucsf.edu


Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Identification of the Last Cog in a Ligand-Independent Signaling Machine?.
D. L. Wiest (2009)
J. Immunol. 182, 5163-5164
   Full Text »    PDF »
Cutting Edge: Rescue of Pre-TCR but Not Mature TCR Signaling in Mice Expressing Membrane-Targeted SLP-76.
N. A. Bezman, R. G. Baker, L. E. Lenox, M. S. Jordan, and G. A. Koretzky (2009)
J. Immunol. 182, 5183-5187
   Abstract »    Full Text »    PDF »
Contribution of TCR-{beta} Locus and HLA to the Shape of the Mature Human V{beta} Repertoire.
J. J. Melenhorst, M. D. H. Lay, D. A. Price, S. D. Adams, J. Zeilah, E. Sosa, N. F. Hensel, D. Follmann, D. C. Douek, M. P. Davenport, et al. (2008)
J. Immunol. 180, 6484-6489
   Abstract »    Full Text »    PDF »
Identification of CMS as a cytosolic adaptor of the human pT{alpha} chain involved in pre-TCR function.
M. N. Navarro, G. Nusspaumer, P. Fuentes, S. Gonzalez-Garcia, J. Alcain, and M. L. Toribio (2007)
Blood 110, 4331-4340
   Abstract »    Full Text »    PDF »
Distinct roles for Syk and ZAP-70 during early thymocyte development.
E. H. Palacios and A. Weiss (2007)
J. Exp. Med. 204, 1703-1715
   Abstract »    Full Text »    PDF »
Changes in the Role of the CD45 Protein Tyrosine Phosphatase in Regulating Lck Tyrosine Phosphorylation during Thymic Development.
R. Falahati and D. Leitenberg (2007)
J. Immunol. 178, 2056-2064
   Abstract »    Full Text »    PDF »
Constitutive expression of the pre-TCR enables development of mature T cells.
S. Schnell, C. Demolliere, P. van den Berk, J. Kirberg, and H. Jacobs (2006)
Int. Immunol. 18, 911-920
   Abstract »    Full Text »    PDF »
Antigen challenge inhibits thymic emigration..
A. P. Uldrich, S. P. Berzins, M. A. Malin, P. Bouillet, A. Strasser, M. J. Smyth, R. L. Boyd, and D. I. Godfrey (2006)
J. Immunol. 176, 4553-4561
   Abstract »    Full Text »    PDF »
Src-like adaptor protein down-regulates T cell receptor (TCR)-CD3 expression by targeting TCR{zeta} for degradation.
M. D. Myers, L. L. Dragone, and A. Weiss (2005)
J. Cell Biol. 170, 285-294
   Abstract »    Full Text »    PDF »
An orderly inactivation of intracellular retention signals controls surface expression of the T cell antigen receptor.
P. Delgado and B. Alarcon (2005)
J. Exp. Med. 201, 555-566
   Abstract »    Full Text »    PDF »
Defined {alpha}{beta} T Cell Receptors with Distinct Ligand Specificities Do Not Require Those Ligands to Signal Double Negative Thymocyte Differentiation.
B. Erman, T. I. Guinter, and A. Singer (2004)
J. Exp. Med. 199, 1719-1724
   Abstract »    Full Text »    PDF »
Obligatory Role for Cooperative Signaling by Pre-TCR and Notch during Thymocyte Differentiation.
M. Ciofani, T. M. Schmitt, A. Ciofani, A. M. Michie, N. Cuburu, A. Aublin, J. L. Maryanski, and J. C. Zuniga-Pflucker (2004)
J. Immunol. 172, 5230-5239
   Abstract »    Full Text »    PDF »
Pre-TCR{alpha} and TCR{alpha} Are Not Interchangeable Partners of TCR{beta} during T Lymphocyte Development.
C. Borowski, X. Li, I. Aifantis, F. Gounari, and H. von Boehmer (2004)
J. Exp. Med. 199, 607-615
   Abstract »    Full Text »    PDF »
The Cytoplasmic Domain of Ig{alpha} Is Necessary and Sufficient to Support Efficient Early B Cell Development.
K. A. Pike, S. Iacampo, J. E. Friedmann, and M. J. H. Ratcliffe (2004)
J. Immunol. 172, 2210-2218
   Abstract »    Full Text »    PDF »
A Role for the Cytoplasmic Tail of the Pre-T Cell Receptor (TCR) alpha Chain in Promoting Constitutive Internalization and Degradation of the Pre-TCR.
Y. R. Carrasco, M. N. Navarro, and M. L. Toribio (2003)
J. Biol. Chem. 278, 14507-14513
   Abstract »    Full Text »    PDF »
Low Activation Threshold As a Mechanism for Ligand-Independent Signaling in Pre-T Cells.
M. C. Haks, S. M. Belkowski, M. Ciofani, M. Rhodes, J. M. Lefebvre, S. Trop, P. Hugo, J. C. Zuniga-Pflucker, and D. L. Wiest (2003)
J. Immunol. 170, 2853-2861
   Abstract »    Full Text »    PDF »
Essential role for Vav1 in activation, but not development, of {gamma}{delta} T cells.
W. Swat, R. Xavier, A. Mizoguchi, E. Mizoguchi, J. Fredericks, K. Fujikawa, A. K. Bhan, and F. W. Alt (2003)
Int. Immunol. 15, 215-221
   Abstract »    Full Text »    PDF »
Positive Selection by the Pre-TCR Yields Mature CD8+ T Cells.
Y. Ito, S. Arai, N. S. C. van Oers, I. Aifantis, H. von Boehmer, and T. Miyazaki (2002)
J. Immunol. 169, 4913-4919
   Abstract »    Full Text »    PDF »
Constitutive Endocytosis and Degradation of the Pre-T Cell Receptor.
M. Panigada, S. Porcellini, E. Barbier, S. Hoeflinger, P.-A. Cazenave, H. Gu, H. Band, H. von Boehmer, and F. Grassi (2002)
J. Exp. Med. 195, 1585-1597
   Abstract »    Full Text »    PDF »
Involvement of the TCR C{beta} FG Loop in Thymic Selection and T Cell Function.
T. Sasada, M. Touma, H.-C. Chang, L. K. Clayton, J.-h. Wang, and E. L. Reinherz (2002)
J. Exp. Med. 195, 1419-1431
   Abstract »    Full Text »    PDF »
The variable, CH1, CH2 and CH3 domains of Ig heavy chain are dispensable for pre-BCR function in transgenic mice.
S. A. Muljo and M. S. Schlissel (2002)
Int. Immunol. 14, 577-584
   Abstract »    Full Text »    PDF »
TCR{beta} Transmembrane Tyrosines Are Required for Pre-TCR Function.
L. M. Spain and P. Liu (2002)
J. Immunol. 168, 127-133
   Abstract »    Full Text »    PDF »
Ligand-independent Signaling Functions for the B Lymphocyte Antigen Receptor and Their Role in Positive Selection during B Lymphopoiesis.
G. Bannish, E. M. Fuentes-Panana, J. C. Cambier, W. S. Pear, and J. G. Monroe (2001)
J. Exp. Med. 194, 1583-1596
   Abstract »    Full Text »    PDF »
Dysregulated Expression of Pre-T{alpha} Reveals the Opposite Effects of Pre-TCR at Successive Stages of T Cell Development.
H. D. Lacorazza, H. E. Porritt, and J. Nikolich-Zugich (2001)
J. Immunol. 167, 5689-5696
   Abstract »    Full Text »    PDF »
Differential Developmental Regulation and Functional Effects on Pre-TCR Surface Expression of Human pT{alpha}a and pT{alpha}b Spliced Isoforms.
A. R. Ramiro, M. N. Navarro, A. Carreira, Y. R. Carrasco, V. G. de Yebenes, G. Carrillo, J. L. San Millan, B. Rubin, and M. L. Toribio (2001)
J. Immunol. 167, 5106-5114
   Abstract »    Full Text »    PDF »
Analysis of Thymocyte Development Reveals That the Gtpase Rhoa Is a Positive Regulator of T Cell Receptor Responses in Vivo.
I. Corre, M. Gomez, S. Vielkind, and D. A. Cantrell (2001)
J. Exp. Med. 194, 903-914
   Abstract »    Full Text »    PDF »
The Biological Activity of Natural and Mutant Pt{alpha} Alleles.
D. Gibbons, N. C. Douglas, D. F. Barber, Q. Liu, R. Sullo, L. Geng, H.-J. Fehling, H. von Boehmer, and A. C. Hayday (2001)
J. Exp. Med. 194, 695-704
   Abstract »    Full Text »    PDF »
An Endoplasmic Reticulum Retention Function for the Cytoplasmic Tail of the Human Pre-T Cell Receptor (Tcr) {alpha} Chain: Potential Role in the Regulation of Cell Surface Pre-Tcr Expression Levels.
Y. R. Carrasco, A. R. Ramiro, C. Trigueros, V. G. de Yebenes, M. Garcia-Peydro, and M. L. Toribio (2001)
J. Exp. Med. 193, 1045-1058
   Abstract »    Full Text »    PDF »
Opposite Ability of Pre-TCR and {{alpha}}{{beta}}TCR to Induce Apoptosis.
A.-M. Steff, S. Trop, M. Maira, J. Drouin, and P. Hugo (2001)
J. Immunol. 166, 5044-5050
   Abstract »    Full Text »    PDF »
Expression of a V Region-Less B Cell Receptor Confers a Tolerance-Like Phenotype on Transgenic B Cells.
D. Corcos, A. Grandien, A. Vazquez, O. Dunda, P. Lores, and D. Bucchini (2001)
J. Immunol. 166, 3083-3089
   Abstract »    Full Text »    PDF »
A Critical Role for CD2 in Both Thymic Selection Events and Mature T Cell Function.
T. Sasada and E. L. Reinherz (2001)
J. Immunol. 166, 2394-2403
   Abstract »    Full Text »    PDF »
Biased V{beta} Usage in Immature Thymocytes Is Independent of DJ{beta} Proximity and pT{{alpha}} Pairing.
A. Wilson, C. Marechal, and H. R. MacDonald (2001)
J. Immunol. 166, 51-57
   Abstract »    Full Text »    PDF »
Competitive Displacement of pT{alpha} by TCR-{alpha} During TCR Assembly Prevents Surface Coexpression of Pre-TCR and {alpha}{beta} TCR.
S. Trop, M. Rhodes, D. L. Wiest, P. Hugo, and J. C. Zuniga-Pflucker (2000)
J. Immunol. 165, 5566-5572
   Abstract »    Full Text »    PDF »
Identification of a novel pre-TCR isoform in which the accessibility of the TCR{beta} subunit is determined by occupancy of the `missing' V domain of pre-T{alpha}.
M. A. Berger, M. Carleton, M. Rhodes, J. M. Sauder, S. Trop, R. L. Dunbrack, P. Hugo, and D. L. Wiest (2000)
Int. Immunol. 12, 1579-1591
   Abstract »    Full Text »    PDF »
Early Onset of CD8 Transgene Expression Inhibits the Transition from DN3 to DP Thymocytes.
A. Wack, M. Coles, T. Norton, A. Hostert, and D. Kioussis (2000)
J. Immunol. 165, 1236-1242
   Abstract »    Full Text »    PDF »
Affiliation to mature B cell repertoire and positive selection can be separated in two distinct processes.
S. Hachemi-Rachedi, A.-M. Drapier, P.-A. Cazenave, and P. Sanchez (2000)
Int. Immunol. 12, 385-395
   Abstract »    Full Text »    PDF »
Murine CCR9, a Chemokine Receptor for Thymus-Expressed Chemokine That Is Up-Regulated Following Pre-TCR Signaling.
A. M. Norment, L. Y. Bogatzki, B. N. Gantner, and M. J. Bevan (2000)
J. Immunol. 164, 639-648
   Abstract »    Full Text »    PDF »
Impaired Anti-Viral T Cell Responses Due to Expression of the LY49A Inhibitory Receptor.
A. J. Zajac, R. E. Vance, W. Held, D. J. D. Sourdive, J. D. Altman, D. H. Raulet, and R. Ahmed (1999)
J. Immunol. 163, 5526-5534
   Abstract »    Full Text »    PDF »
Persistence of Memory CD8 T Cells in MHC Class I-Deficient Mice.
K. Murali-Krishna, L. L. Lau, S. Sambhara, F. Lemonnier, J. Altman, and R. Ahmed (1999)
Science 286, 1377-1381
   Abstract »    Full Text »
Allelic Exclusion of the T Cell Receptor {beta} Locus Requires the Sh2 Domain-Containing Leukocyte Protein (Slp)-76 Adaptor Protein.
I. Aifantis, V. I. Pivniouk, F. Gartner, J. Feinberg, W. Swat, F. W. Alt, H. von Boehmer, and R. S. Geha (1999)
J. Exp. Med. 190, 1093-1102
   Abstract »    Full Text »    PDF »
Development of B cells expressing surface immunoglobulin molecules that lack V(D)J-encoded determinants in the avian embryo bursa of Fabricius.
C. E. Sayegh, S. L. Demaries, S. Iacampo, and M. J. H. Ratcliffe (1999)
PNAS 96, 10806-10811
   Abstract »    Full Text »    PDF »
Signals Transduced by CD3{epsilon}, But Not by Surface Pre-TCR Complexes, Are Able to Induce Maturation of an Early Thymic Lymphoma In Vitro.
M. Carleton, N. R. Ruetsch, M. A. Berger, M. Rhodes, S. Kaptik, and D. L. Wiest (1999)
J. Immunol. 163, 2576-2585
   Abstract »    Full Text »    PDF »
Pre-T Cell Receptor Signals Are Responsible for the Down-Regulation of Syk Protein Tyrosine Kinase Expression.
D. H. Chu, N. S. C. van Oers, M. Malissen, J. Harris, M. Elder, and A. Weiss (1999)
J. Immunol. 163, 2610-2620
   Abstract »    Full Text »    PDF »
Regulation of T cell receptor (TCR) beta  gene expression by CD3 complex signaling in immature thymocytes: Implications for TCRbeta allelic exclusion.
J. Biro, A. Wurch, A. J. Potocnik, I. Falk, H. Mossmann, and K. Eichmann (1999)
PNAS 96, 3882-3887
   Abstract »    Full Text »    PDF »
The Impact of Pre-T-cell Receptor Signals on Gene Expression in Developing T Cells.
H. VON BOEHMER, I. AIFANTIS, O. AZOGUI, C. SAINT-RUF, and F. GRASSI (1999)
Cold Spring Harb Symp Quant Biol 64, 283-290
   Abstract »    PDF »
Role of NF-{kappa}B in T-lymphocyte Development.
R.E. VOLL and S. GHOSH (1999)
Cold Spring Harb Symp Quant Biol 64, 485-490
   Abstract »    PDF »
Requirement of CD3 Complex-associated Signaling Functions for Expression of Rearranged T Cell Receptor {beta} VDJ Genes in Early Thymic Development.
A. Wurch, J. Biro, A. J. Potocnik, I. Falk, H. Mossmann, and K. Eichmann (1998)
J. Exp. Med. 188, 1669-1678
   Abstract »    Full Text »    PDF »
Identification of a Late Stage of Small Noncycling pT{alpha}- Pre-T Cells as Immediate Precursors of T Cell Receptor {alpha}/{beta}+ Thymocytes.
C. Trigueros, A. R. Ramiro, Y. R. Carrasco, V. G. de Yebenes, J. P. Albar, and M. L. Toribio (1998)
J. Exp. Med. 188, 1401-1412
   Abstract »    Full Text »    PDF »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)