title: Limited combinatorial repertoire of gamma delta T-cell receptors expressed by T-cell acute lymphoblastic leukemias.
abstract: Detailed analysis of the rearrangement and expression of T-cell receptor gamma (TcR-gamma) and TcR-delta genes was performed in ten TcR-gamma delta+ T-cell acute lymphoblastic leukemias (T-ALL). In nine T-ALL the TcR-gamma genes were rearranged on both alleles, whereas in the tenth leukemia one allele was rearranged and the other was in germline configuration. Twelve out of the 19 rearranged alleles contained rearrangements of the J gamma 2.3 gene segment, five of which were to the V gamma 8 gene segment and three to the V gamma 3 gene segment. This implies that the combinatorial repertoire of the rearranged TcR-gamma gene is restricted due to the preferential usage of several V gamma and J gamma gene segments. The TcR-delta genes were rearranged on both alleles in nine T-ALL, whereas in the tenth leukemia one allele was rearranged and the other deleted. The combinatorial repertoire of the TcR-delta genes was homogeneous, as in all ten T-ALL at least one allele contained a V delta 1-J delta 1 rearrangement. In at least nine of the ten T-ALL the V delta 1-J delta 1 allele coded for the expressed TcR-delta chain, as was supported by reactivity with the anti-V delta 1-J delta 1 (delta TCS1) antibody in all T-ALL tested. As the total repertoire of the TcR molecules is not only dependent on combinations of gene segments, but also on the size and diversity of the junctional regions, we studied the V delta 1-J delta 1 junctional regions using the polymerase chain reaction (PCR) technique. These PCR analyses showed that the size of the V delta 1-J delta 1 junctional regions differed markedly (up to approximately 30 bases or more) between the leukemias. Therefore we conclude that the combinatorial repertoire of TcR-delta S+ T-ALL is limited, especially due to the homogeneous TcR-gamma gene rearrangements, but that the junctional repertoire of the TcR-delta genes seems to be extensive.
authors.affiliation: Department of Immunology, Erasmus University/University Hospital Dijkzigt, Rotterdam, The Netherlands.
authors.forename: T M
authors.initials: TM
authors.lastname: Breit
authors.forename: I L
authors.initials: IL
authors.lastname: Wolvers-Tettero
authors.forename: K
authors.initials: K
authors.lastname: Hählen
authors.forename: E R
authors.initials: ER
authors.lastname: van Wering
authors.forename: J J
authors.initials: JJ
authors.lastname: van Dongen
mesh_terms: D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002874:Chromosome Mapping; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D016130:Immunophenotyping; D007945:Leukemia, Lymphoid / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics*; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta