Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 335K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Pasqual, N. Articles by Jouvin-Marche, E. Search for Related Content PubMed PubMed Citation Articles by Pasqual, N. Articles by Jouvin-Marche, E. Social Bookmarking                            What's this?

Quantitative and Qualitative Changes in V-J Rearrangements During Mouse Thymocytes Differentiation : Implication For a Limited T Cell Receptor Chain Repertoire

Nicolas Pasqual¹, Maighréad Gallagher¹, Catherine Aude-Garcia¹, Mélanie Loiodice¹, Florence Thuderoz², Jacques Demongeot², Rod Ceredig¹, Patrice Noël Marche¹ and Evelyne Jouvin-Marche¹

¹ Laboratoire d'Immunochimie, Commissariat à l'Energie Atomique, Institut National de la Santé et de la Recherche Médicale, Unité 548, Université Joseph Fourier, 38054 Grenoble Cedex 9, France
² Technique pour l'Imagerie, la Modélisation et la Cognition, Université J Fourier Grenoble, Faculté de Médecine, 38700 la Tronche, France

Address correspondence to Dr. Evelyne Jouvin-Marche, Laboratoire d'Immunochimie CEA-G/DRDC/ICH, 17 rue des Martyrs, 38054 Grenoble Cedex 9, France. Phone: 33-4-3878-5770; Fax: 33-4-3878-9803; E-mail: immuno{at}dsvsud.cea.fr

Knowledge of the complete nucleotide sequence of the mouse TCRAD locus allows an accurate determination V-J rearrangement status. Using multiplex genomic PCR assays and real time PCR analysis, we report a comprehensive and systematic analysis of the V-J recombination of TCR chain in normal mouse thymocytes during development. These respective qualitative and quantitative approaches give rise to four major points describing the control of gene rearrangements. (a) The V-J recombination pattern is not random during ontogeny and generates a limited TCR repertoire; (b) V-J rearrangement control is intrinsic to the thymus; (c) each V gene rearranges to a set of contiguous J segments with a gaussian-like frequency; (d) there are more rearrangements involving V genes at the 3' side than 5' end of V region. Taken together, this reflects a preferential association of V and J gene segments according to their respective positions in the locus, indicating that accessibility of both V and J regions is coordinately regulated, but in different ways. These results provide a new insight into TCR repertoire size and suggest a scenario for V usage during differentiation.

Key Words: TCR-diversity • TCRAD locus • rearrangement • development • quantitative PCR

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Ferreira, C., Singh, Y., Furmanski, A. L., Wong, F. S., Garden, O. A., Dyson, J. (2009). Non-obese diabetic mice select a low-diversity repertoire of natural regulatory T cells. Proc. Natl. Acad. Sci. USA 106: 8320-8325 [Abstract] [Full Text]  
• Hendricks, D. W., Fink, P. J. (2009). Uneven Colonization of the Lymphoid Periphery by T Cells That Undergo Early TCR{alpha} Rearrangements. J. Immunol. 182: 4267-4274 [Abstract] [Full Text]  
• Gobert, M., Treilleux, I., Bendriss-Vermare, N., Bachelot, T., Goddard-Leon, S., Arfi, V., Biota, C., Doffin, A. C., Durand, I., Olive, D., Perez, S., Pasqual, N., Faure, C., Ray-Coquard, I., Puisieux, A., Caux, C., Blay, J.-Y., Menetrier-Caux, C. (2009). Regulatory T Cells Recruited through CCL22/CCR4 Are Selectively Activated in Lymphoid Infiltrates Surrounding Primary Breast Tumors and Lead to an Adverse Clinical Outcome. Cancer Res. 69: 2000-2009 [Abstract] [Full Text]  
• Furmanski, A. L., Ferreira, C., Bartok, I., Dimakou, S., Rice, J., Stevenson, F. K., Millrain, M. M., Simpson, E., Dyson, J. (2008). Public T Cell Receptor -Chains Are Not Advantaged during Positive Selection. J. Immunol. 180: 1029-1039 [Abstract] [Full Text]  
• Hager, E., Hawwari, A., Matsuda, J. L., Krangel, M. S., Gapin, L. (2007). Multiple Constraints at the Level of TCR{alpha} Rearrangement Impact V{alpha}14i NKT Cell Development. J. Immunol. 179: 2228-2234 [Abstract] [Full Text]  
• Warmflash, A., Dinner, A. R. (2006). A Model for TCR Gene Segment Use. J. Immunol. 177: 3857-3864 [Abstract] [Full Text]  
• Ferreira, C., Furmanski, A., Millrain, M., Bartok, I., Guillaume, P., Lees, R., Simpson, E., MacDonald, H. R., Dyson, J. (2006). TCR-{alpha} CDR3 Loop Audition Regulates Positive Selection. J. Immunol. 177: 2477-2485 [Abstract] [Full Text]  
• Hawwari, A., Krangel, M. S. (2005). Regulation of TCR {delta} and {alpha} repertoires by local and long-distance control of variable gene segment chromatin structure. JEM 202: 467-472 [Abstract] [Full Text]  
• Baum, T.-P., Pasqual, N., Thuderoz, F., Hierle, V., Chaume, D., Lefranc, M.-P., Jouvin-Marche, E., Marche, P.-N., Demongeot, J. (2004). IMGT/GeneInfo: enhancing V(D)J recombination database accessibility. Nucleic Acids Res 32: D51-54 [Abstract] [Full Text]  
• Holman, P. O., Walsh, E. R., Hogquist, K. A. (2003). The Central Tolerance Response to Male Antigen in Normal Mice Is Deletion and Not Receptor Editing. J. Immunol. 171: 4048-4053 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS