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Mechanisms Controlling Termination of V-J Recombination at the TCR Locus: Implications for Allelic and Isotypic Exclusion of TCR Chains¹

Laurent Boucontet^*, Nuno Sepúlveda, Jorge Carneiro and Pablo Pereira^2,*

^* Unité du Développement des Lymphocytes, Centre National de la Recherche Scientifique Unité de Recherche Associée 1961, Institut Pasteur, Paris, France; Instituto Gulbenkian de Ciencia, Oeiras, Portugal

Analyses of V-J rearrangements producing the most commonly expressed TCR chains in over 200 TCR⁺ thymocytes showed that assembly of TCR V-region genes display properties of allelic exclusion. Moreover, introduction of functionally rearranged TCR and transgenes results in a profound inhibition of endogenous TCR rearrangements in progenitor cells. The extent of TCR rearrangements in these cells is best explained by a model in which initiation of TCR rearrangements at both alleles is asymmetric, occurs at different frequencies depending on the V or J segments involved, and is terminated upon production of a functional TCR. Approximately 10% of the cells studied contained two functional TCR chains involving different V and J gene segments, thus defining a certain degree of isotypic inclusion. However, these cells are isotypically excluded at the level of cell surface expression possibly due to pairing restrictions between different TCR and chains.

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