Mechanisms controlling termination of V-J recombination at the TCRgamma locus: implications for allelic and isotypic exclusion of TCRgamma chains.
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.
Boucontet
Laurent
L
Unité du Développement des Lymphocytes, Centre National de la Recherche Scientifique Unité de Recherche Associée 1961, Institut Pasteur, Paris, France.
Sepúlveda
Nuno
N
Carneiro
Jorge
J
Pereira
Pablo
P
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
D016692:Receptors, Antigen, T-Cell, gamma-delta