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 16 August 1991:
Vol. 253. no. 5021, pp. 778 - 781
DOI: 10.1126/science.1831564
Prev | Table of Contents | Next

Articles

Science, Vol 253, Issue 5021, 778-781
Copyright © 1991 by American Association for the Advancement of Science

articles

Thymocyte expression of RAG-1 and RAG-2: termination by T cell receptor cross-linking

LA Turka, DG Schatz, MA Oettinger, JJ Chun, C Gorka, K Lee, WT McCormack, and CB Thompson

Department of Internal Medicine, University of Michigan, Ann Arbor 48109.

The expression of the V(D)J [variable (diversity) joining elements] recombination activating genes, RAG-1 and RAG-2, has been examined during T cell development in the thymus. In situ hybridization to intact thymus and RNA blot analysis of isolated thymic subpopulations separated on the basis of T cell receptor (TCR) expression demonstrated that both TCR- and TCR+ cortical thymocytes express RAG-1 and RAG-2 messenger RNA's. Within the TCR+ population, RAG expression was observed in immature CD4+CD8+ (double positive) cells, but not in the more mature CD4+CD8- or CD4-CD8+ (single positive) subpopulations. Thus, although cortical thymocytes that bear TCR on their surface continue to express RAG-1 and RAG-2, it appears that the expression of both genes is normally terminated during subsequent thymic maturation. Since thymocyte maturation in vivo is thought to be regulated through the interaction of the TCR complex with self major histocompatibility complex (MHC) antigens, these data suggest that signals transduced by the TCR complex might result in the termination of RAG expression. Consistent with this hypothesis, thymocyte TCR cross-linking in vitro led to rapid termination of RAG-1 and RAG-2 expression, whereas cross-linking of other T cell surface antigens such as CD4, CD8, or HLA class I had no effect.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Cutting Edge: Highly Alloreactive Dual TCR T Cells Play a Dominant Role in Graft-versus-Host Disease.
G. P. Morris and P. M. Allen (2009)
J. Immunol. 182, 6639-6643
   Abstract »    Full Text »    PDF »
Development of all CD4 T lineages requires nuclear factor TOX.
P. Aliahmad and J. Kaye (2008)
J. Exp. Med. 205, 245-256
   Abstract »    Full Text »    PDF »
Transcriptional Analysis of Clonal Deletion In Vivo.
T. A. Baldwin and K. A. Hogquist (2007)
J. Immunol. 179, 837-844
   Abstract »    Full Text »    PDF »
Role for rearranged variable gene segments in directing secondary T cell receptor {alpha} recombination.
A. Hawwari and M. S. Krangel (2007)
PNAS 104, 903-907
   Abstract »    Full Text »    PDF »
Revision of T cell receptor {alpha} chain genes is required for normal T lymphocyte development.
C.-Y. Huang, B. P. Sleckman, and O. Kanagawa (2005)
PNAS 102, 14356-14361
   Abstract »    Full Text »    PDF »
Suppression of apoptosis by bcl-2 overexpression in lymphoid cells of transgenic zebrafish.
D. M. Langenau, C. Jette, S. Berghmans, T. Palomero, J. P. Kanki, J. L. Kutok, and A. T. Look (2005)
Blood 105, 3278-3285
   Abstract »    Full Text »    PDF »
T cells from epicutaneously immunized mice are prone to T cell receptor revision.
M. S. Bynoe, C. Viret, R. A. Flavell, and C. A. Janeway Jr. (2005)
PNAS 102, 2898-2903
   Abstract »    Full Text »    PDF »
The Regulated Expression of a Diverse Set of Genes during Thymocyte Positive Selection In Vivo.
V. E. Mick, T. K. Starr, T. M. McCaughtry, L. K. McNeil, and K. A. Hogquist (2004)
J. Immunol. 173, 5434-5444
   Abstract »    Full Text »    PDF »
Exclusion and Inclusion of TCR{alpha} Proteins during T Cell Development in TCR-Transgenic and Normal Mice.
H. D. Lacorazza and J. Nikolich-Zugich (2004)
J. Immunol. 173, 5591-5600
   Abstract »    Full Text »    PDF »
Distinct transcriptional programs in thymocytes responding to T cell receptor, Notch, and positive selection signals.
Y. H. Huang, D. Li, A. Winoto, and E. A. Robey (2004)
PNAS 101, 4936-4941
   Abstract »    Full Text »    PDF »
T Cell Receptor Revision Does Not Solely Target Recent Thymic Emigrants.
C. J. Cooper, M. T. Orr, C. J. McMahan, and P. J. Fink (2003)
J. Immunol. 171, 226-233
   Abstract »    Full Text »    PDF »
Cutting Edge: CD40-Induced Expression of Recombination Activating Gene (RAG) 1 and RAG2: A Mechanism for the Generation of Autoaggressive T Cells in the Periphery.
G. M. Vaitaitis, M. Poulin, R. J. Sanderson, K. Haskins, and D. H. Wagner Jr. (2003)
J. Immunol. 170, 3455-3459
   Abstract »    Full Text »    PDF »
Expression of recombination-activating gene in mature peripheral T cells in Peyer's patch.
E. Kondo, H. Wakao, H. Koseki, T. Takemori, S. Kojo, M. Harada, M. Takahashi, S. Sakata, C. Shimizu, T. Ito, et al. (2003)
Int. Immunol. 15, 393-402
   Abstract »    Full Text »    PDF »
Restricting Zap70 Expression to CD4+CD8+ Thymocytes Reveals a T Cell Receptor-dependent Proofreading Mechanism Controlling the Completion of Positive Selection.
X. Liu, A. Adams, K. F. Wildt, B. Aronow, L. Feigenbaum, and R. Bosselut (2003)
J. Exp. Med. 197, 363-373
   Abstract »    Full Text »    PDF »
Dynamic Tuning of T Cell Reactivity by Self-Peptide-Major Histocompatibility Complex Ligands.
P. Wong, G. M. Barton, K. A. Forbush, and A. Y. Rudensky (2001)
J. Exp. Med. 193, 1179-1188
   Abstract »    Full Text »    PDF »
c-Myb Binds to a Sequence in the Proximal Region of the RAG-2 Promoter and Is Essential for Promoter Activity in T-Lineage Cells.
Q.-F. Wang, J. Lauring, and M. S. Schlissel (2000)
Mol. Cell. Biol. 20, 9203-9211
   Abstract »    Full Text »
Receptor Revision in Peripheral T Cells Creates a Diverse V{beta} Repertoire.
C. J. McMahan and P. J. Fink (2000)
J. Immunol. 165, 6902-6907
   Abstract »    Full Text »    PDF »
Response to RAG-Mediated V(D)J Cleavage by NBS1 and {gamma}-H2AX.
H. T. Chen, A. Bhandoola, M. J. Difilippantonio, J. Zhu, M. J. Brown, X. Tai, E. P. Rogakou, T. M. Brotz, W. M. Bonner, T. Ried, et al. (2000)
Science 290, 1962-1964
   Abstract »    Full Text »
Competition for Specific Intrathymic Ligands Limits Positive Selection in a TCR Transgenic Model of CD4+ T Cell Development.
P. Wong, A. W. Goldrath, and A. Y. Rudensky (2000)
J. Immunol. 164, 6252-6259
   Abstract »    Full Text »    PDF »
Cutting Edge: Recombinase-Activating Gene Expression and V(D)J Recombination in CD4+CD3low Mature T Lymphocytes.
E. Lantelme, B. Palermo, L. Granziero, S. Mantovani, R. Campanelli, V. Monafo, A. Lanzavecchia, and C. Giachino (2000)
J. Immunol. 164, 3455-3459
   Abstract »    Full Text »    PDF »
Thymocyte Maturation Is Regulated by the Activity of the Helix-Loop-Helix Protein, E47.
G. Bain, M. W. Quong, R. S. Soloff, S. M. Hedrick, and C. Murre (1999)
J. Exp. Med. 190, 1605-1616
   Abstract »    Full Text »    PDF »
RAG2 is regulated differentially in B and T cells by elements 5' of the promoter.
R. J. Monroe, F. Chen, R. Ferrini, L. Davidson, and F. W. Alt (1999)
PNAS 96, 12713-12718
   Abstract »    Full Text »    PDF »
Coordinate Regulation of RAG1 and RAG2 by Cell Type-Specific DNA Elements 5' of RAG2.
W. Yu, Z. Misulovin, H. Suh, R. R. Hardy, M. Jankovic, N. Yannoutsos, and M. C. Nussenzweig (1999)
Science 285, 1080-1084
   Abstract »    Full Text »
Distinct Factors Regulate the Murine RAG-2 Promoter in B- and T-Cell Lines.
J. Lauring and M. S. Schlissel (1999)
Mol. Cell. Biol. 19, 2601-2612
   Abstract »    Full Text »    PDF »
A Conserved Sequence Block in the Murine and Human TCR J{alpha} Region: Assessment of Regulatory Function In Vivo.
P. Riegert and S. Gilfillan (1999)
J. Immunol. 162, 3471-3480
   Abstract »    Full Text »    PDF »
RAG Expression in B Cells in Secondary Lymphoid Tissues.
W. YU, H. NAGAOKA, Z. MISULOVIN, E. MEFFRE, H. SUH, M. JANKOVIC, N. YANNOUTSOS, R. CASELLAS, E. BESMER, F. PAPAVASILIOU, et al. (1999)
Cold Spring Harb Symp Quant Biol 64, 207-210
   Abstract »    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 »
Rapid deletion of rearranged T cell antigen receptor (TCR) Valpha -Jalpha segment by secondary rearrangement in the thymus: Role of continuous rearrangement of TCR alpha  chain gene and positive selection in the T cell repertoire formation.
F. Wang, C.-Y. Huang, and O. Kanagawa (1998)
PNAS 95, 11834-11839
   Abstract »    Full Text »    PDF »
Highly Restricted T Cell Repertoire Shaped by a Single Major Histocompatibility Complex-Peptide Ligand in the Presence of a Single Rearranged T Cell Receptor {beta} Chain.
Y. Fukui, O. Hashimoto, A. Inayoshi, T. Gyotoku, T. Sano, T. Koga, T. Gushima, and T. Sasazuki (1998)
J. Exp. Med. 188, 897-907
   Abstract »    Full Text »    PDF »
Receptor-Specific Allelic Exclusion of TCRV{alpha}-Chains During Development.
R. Boyd, I. Kozieradzki, A. Chidgey, H.-W. Mittrucker, D. Bouchard, E. Timms, K. Kishihara, C. J. Ong, D. Chui, J. D. Marth, et al. (1998)
J. Immunol. 161, 1718-1727
   Abstract »    Full Text »    PDF »
Cross-lineage expression of Ig-beta (B29) in thymocytes: Positive and negative gene regulation to establish T cell identity.
H. Wang, R. A. Diamond, and E. V. Rothenberg (1998)
PNAS 95, 6831-6836
   Abstract »    Full Text »    PDF »
Changes in Locus-specific V(D)J Recombinase Activity Induced by Immunoglobulin Gene Products during B Cell Development.
A. Constantinescu and M. S. Schlissel (1997)
J. Exp. Med. 185, 609-620
   Abstract »    Full Text »    PDF »
Productive T-cell receptor beta-chain gene rearrangement: coincident regulation of cell cycle and clonality during development in vivo..
E S Hoffman, L Passoni, T Crompton, T M Leu, D G Schatz, A Koff, M J Owen, and A C Hayday (1996)
Genes & Dev. 10, 948-962
   Abstract »    PDF »
NFATc3, a Lymphoid-specific NFATc Family Member That Is Calcium-regulated and Exhibits Distinct DNA Binding Specificity.
S. N. Ho, D. J. Thomas, L. A. Timmerman, X. Li, U. Francke, and G. R. Crabtree (1995)
J. Biol. Chem. 270, 19898-19907
   Abstract »    Full Text »    PDF »
Role of TCR zeta chain in T cell development and selection.
E. Shores, K Huang, T Tran, E Lee, A Grinberg, and P. Love (1994)
Science 266, 1047-1050
   Abstract »    PDF »
Functional immunoglobulin transgenes guide ordered B-cell differentiation in Rag-1-deficient mice..
E Spanopoulou, C A Roman, L M Corcoran, M S Schlissel, D P Silver, D Nemazee, M C Nussenzweig, S A Shinton, R R Hardy, and D Baltimore (1994)
Genes & Dev. 8, 1030-1042
   Abstract »    PDF »
Expression of two T cell receptor alpha chains: dual receptor T cells.
E Padovan, G Casorati, P Dellabona, S Meyer, M Brockhaus, and A Lanzavecchia (1993)
Science 262, 422-424
   Abstract »    PDF »
Surface expression of two distinct functional antigen receptors on human gamma delta T cells.
F Davodeau, M. Peyrat, I Houde, M. Hallet, G De Libero, H Vie, and M Bonneville (1993)
Science 260, 1800-1802
   Abstract »    PDF »
Regulation of V(D)J recombination activator protein RAG-2 by phosphorylation.
W. Lin and S Desiderio (1993)
Science 260, 953-959
   Abstract »    PDF »
Post-transcriptional regulation of early T cell development by T cell receptor signals.
Y Takahama and A Singer (1992)
Science 258, 1456-1462
   Abstract »    PDF »


To Advertise     Find Products

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