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The Journal of Immunology, 2005, 174: 3912-3919.
Copyright © 2005 by The American Association of Immunologists

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

Laurent Boucontet*, Nuno Sepúlveda{dagger}, Jorge Carneiro{dagger} and Pablo Pereira2,*

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

Analyses of V{gamma}-J{gamma} rearrangements producing the most commonly expressed TCR{gamma} chains in over 200 {gamma}{delta} TCR+ thymocytes showed that assembly of TCR{gamma} V-region genes display properties of allelic exclusion. Moreover, introduction of functionally rearranged TCR{gamma} and {delta} transgenes results in a profound inhibition of endogenous TCR{gamma} rearrangements in progenitor cells. The extent of TCR{gamma} rearrangements in these cells is best explained by a model in which initiation of TCR{gamma} 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 {gamma}{delta} TCR. Approximately 10% of the cells studied contained two functional TCR{gamma} chains involving different V and J{gamma} 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{gamma} and {delta} chains.




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M. L. Joachims, J. L. Chain, S. W. Hooker, C. J. Knott-Craig, and L. F. Thompson
Human {alpha}beta and {gamma}{delta} Thymocyte Development: TCR Gene Rearrangements, Intracellular TCRbeta Expression, and {gamma}{delta} Developmental Potential--Differences between Men and Mice
J. Immunol., February 1, 2006; 176(3): 1543 - 1552.
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