title: Mechanisms controlling termination of V-J recombination at the TCRgamma locus: implications for allelic and isotypic exclusion of TCRgamma chains.
abstract: Analyses of Vgamma-Jgamma rearrangements producing the most commonly expressed TCRgamma chains in over 200 gammadelta TCR(+) thymocytes showed that assembly of TCRgamma V-region genes display properties of allelic exclusion. Moreover, introduction of functionally rearranged TCRgamma and delta transgenes results in a profound inhibition of endogenous TCRgamma rearrangements in progenitor cells. The extent of TCRgamma rearrangements in these cells is best explained by a model in which initiation of TCRgamma 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 gammadelta TCR. Approximately 10% of the cells studied contained two functional TCRgamma chains involving different V and Jgamma 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 TCRgamma and delta chains.
authors.affiliation: Unité du Développement des Lymphocytes, Centre National de la Recherche Scientifique Unité de Recherche Associée 1961, Institut Pasteur, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Boucontet
authors.forename: Nuno
authors.initials: N
authors.lastname: Sepúlveda
authors.forename: Jorge
authors.initials: J
authors.lastname: Carneiro
authors.forename: Pablo
authors.initials: P
authors.lastname: Pereira
mesh_terms: D000483:Alleles; D000818:Animals; D005787:Gene Frequency; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D019675:Genes, T-Cell Receptor gamma; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D019076:Transgenes
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta