© The Rockefeller University Press, 0022-1007/1997/8/767/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 5, August 29, 1997 767-775
Allelic Exclusion in pT
-deficient Mice: No Evidence for Cell Surface Expression of Two T Cell Receptor (TCR)-β Chains, but Less Efficient Inhibition of Endogeneous Vβ
(D)Jβ Rearrangements in the Presence of a Functional TCR-β Transgene
Anna Krotkova*,
Harald von Boehmer
, and
Hans Jörg Fehling*
From the * Basel Institute for Immunology, CH-4005 Basel, Switzerland; and the
Institut Necker, Institut National de la Santé et de la Recherche Medicale 373, F-75730 Paris Cedex 15, France
Although individual T lymphocytes have the potential to generate two distinct T cell receptor (TCR)-β chains, they usually express only one allele, a phenomenon termed allelic exclusion. Expression of a functional TCR-β chain during early T cell development leads to the formation of a pre-T cell receptor (pre-TCR) complex and, at the same developmental stage, arrest of further TCR-β rearrangements, suggesting a role of the pre-TCR in mediating allelic exclusion. To investigate the potential link between pre-TCR formation and inhibition of further TCR-β rearrangements, we have studied the efficiency of allelic exclusion in mice lacking the pre-TCR-
(pT
) chain, a core component of the pre-TCR. Staining of CD3+ thymocytes and lymph node cells with antibodies specific for Vβ6 or Vβ8 and a pool of antibodies specific for most other Vβ elements, did not reveal any violation of allelic exclusion at the level of cell surface expression. This was also true for pT
-deficient mice expressing a functionally rearranged TCR-β transgene. Interestingly, although the transgenic TCR-β chain significantly influenced thymocyte development even in the absence of pT
, it was not able to inhibit fully endogeneous TCR-β rearrangements either in total thymocytes or in sorted CD25+ pre-T cells of pT
–/– mice, clearly indicating an involvement of the pre-TCR in allelic exclusion.
Address correspondence to H.J. Fehling, Basel Institute for Immunology, Grenzacherstrasse 487, CH-4005 Basel, Switzerland. Phone: 41-61-605-1245; FAX: 41-61-605-1364; E-mail: fehling{at}bii.ch
1 Abbreviations used in this paper: BCR, B cell receptor; CS, calf serum; D, diversity; DN, double-negative; DP, double-positive; ES, embryonic stem; FSC, forward scatter; J, joining; PI, propidium iodine; pT
, pre-TCR
; SP, single-positive; SSC, side scatter; V, variable.

CiteULike
Complore
Connotea
Del.icio.us
Digg
Facebook
Reddit
Technorati
Twitter What's this?
This article has been cited by other articles:
-
Carpenter, A. C., Yang-Iott, K. S., Chao, L. H., Nuskey, B., Whitlow, S., Alt, F. W., Bassing, C. H.
(2009). Assembled DJ{beta} Complexes Influence TCR{beta} Chain Selection and Peripheral V{beta} Repertoire. J. Immunol.
182: 5586-5595
[Abstract]
[Full Text]
-
Touma, M., Sun, Z.-Y. J., Clayton, L. K., Marissen, W. E., Kruisbeek, A. M., Wagner, G., Reinherz, E. L.
(2007). Importance of the CD3{gamma} Ectodomain Terminal beta-Strand and Membrane Proximal Stalk in Thymic Development and Receptor Assembly. J. Immunol.
178: 3668-3679
[Abstract]
[Full Text]
-
Touma, M., Chang, H.-C., Sasada, T., Handley, M., Clayton, L. K., Reinherz, E. L.
(2006). The TCR Cbeta FG Loop Regulates {alpha}beta T Cell Development.. J. Immunol.
176: 6812-6823
[Abstract]
[Full Text]
-
Gerber, D., Boucontet, L., Pereira, P.
(2004). Early Expression of a Functional TCR{beta} Chain Inhibits TCR{gamma} Gene Rearrangements without Altering the Frequency of TCR{gamma}{delta} Lineage Cells. J. Immunol.
173: 2516-2523
[Abstract]
[Full Text]
-
Legrand, N., Freitas, A. A.
(2001). CD8+ T Lymphocytes in Double {alpha}{beta} TCR Transgenic Mice. I. TCR Expression and Thymus Selection in the Absence or in the Presence of Self-Antigen. J. Immunol.
167: 6150-6157
[Abstract]
[Full Text]
-
Petersson, K., Ivars, F.
(2001). Early TCR {{alpha}}{{beta}} Expression Promotes Maturation of T Cells Expressing Fc{{epsilon}}RI{{gamma}} Containing TCR/CD3 Complexes. J. Immunol.
166: 6616-6624
[Abstract]
[Full Text]
-
Nishimura, H., Honjo, T., Minato, N.
(2000). Facilitation of {beta} Selection and Modification of Positive Selection in the Thymus of Pd-1-Deficient Mice. JEM
191: 891-898
[Abstract]
[Full Text]
-
Mancini, S., Candeias, S. M., Fehling, H. J., von Boehmer, H., Jouvin-Marche, E., Marche, P. N.
(1999). TCR {alpha}-Chain Repertoire in pT{alpha}-Deficient Mice Is Diverse and Developmentally Regulated: Implications for Pre-TCR Functions and TCRA Gene Rearrangement. J. Immunol.
163: 6053-6059
[Abstract]
[Full Text]
-
Aifantis, I., Pivniouk, V. I., Gartner, F., Feinberg, J., Swat, W., Alt, F. W., von Boehmer, H., Geha, R. S.
(1999). Allelic Exclusion of the T Cell Receptor {beta} Locus Requires the Sh2 Domain-Containing Leukocyte Protein (Slp)-76 Adaptor Protein. JEM
190: 1093-1102
[Abstract]
[Full Text]
-
Biro, J., Wurch, A., Potocnik, A. J., Falk, I., Mossmann, H., Eichmann, K.
(1999). Regulation of T cell receptor (TCR) beta gene expression by CD3 complex signaling in immature thymocytes: Implications for TCRbeta allelic exclusion. Proc. Natl. Acad. Sci. USA
96: 3882-3887
[Abstract]
[Full Text]
-
VON BOEHMER, H., AIFANTIS, I., AZOGUI, O., SAINT-RUF, C., GRASSI, F.
(1999). The Impact of Pre-T-cell Receptor Signals on Gene Expression in Developing T Cells. Cold Spring Harb Symp Quant Biol
64: 283-290
[Abstract]
-
Irving, B. A., Alt, F. W., Killeen, N.
(1998). Thymocyte Development in the Absence of Pre-T Cell Receptor Extracellular Immunoglobulin Domains. Science
280: 905-908
[Abstract]
[Full Text]
-
Ardouin, L., Ismaili, J., Malissen, B., Malissen, M.
(1998). The CD3-{gamma}{delta}{varepsilon} and CD3-{zeta}/{eta} Modules Are Each Essential for Allelic Exclusion at the T Cell Receptor {beta} Locus but Are Both Dispensable for the Initiation of V to (D)J Recombination at the T Cell Receptor-{beta}, -{gamma}, and -{delta} Loci. JEM
187: 105-116
[Abstract]
[Full Text]