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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

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