Organization, structure and evolution of 41kb of genomic DNA spanning the D-J-C region of the sheep TRB locus

Antonacci, Rachele; Tommaso, Silvia Di; Lanave, Cecilia; Cribiu, Edmond; Ciccarese, Salvatrice; Massari, Serafina

doi:10.1016/j.molimm.2007.05.023

Cited by 23 publications

(55 citation statements)

References 38 publications

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“…A previous study on cloning and sequencing of the sheep TRB locus revealed that the D-J-C region is organized in three independent clusters tandem aligned, with D-J-C cluster 3 additional with respect to the other mammalian TRB loci [12]. D-J-C cluster 1 contains one TRBD , six TRBJ and one TRBC gene.…”

Section: Resultsmentioning

confidence: 99%

“…The clones were obtained by RT-PCR. The 5' primer was chosen on the YLCASS amino acid motif of the TRBV genes as members of the TRBV subgroups with this motif which seem to be the most frequently used [16] while the 3'-primer was designed on a conserved region of the three TRBC genes [12]. …”

Section: Resultsmentioning

confidence: 99%

“…In the artiodactyls lineage, i.e., in sheep [12] as well as in cattle [13] and in pig [14], a duplication event within the 3'-end of the TRB locus has led to the generation of a third D-J-C cluster. The presence of an additional cluster produces an increase in the number of D and J genes available to partake in somatic recombination, but also expand the distance between the enhancer (Eβ) and the promoter (PDβ1) elements within the locus.…”

Section: Introductionmentioning

confidence: 99%

“…Surprisingly also, in presence of three D-J-C clusters, both the nucleotide and protein sequences of all three TRBC genes are highly similar. Only four amino acid residues have undergone replacement in the TRBC1 gene with respect to the TRBC2 and TRBC3 genes, while the TRBC3 3'-UTR region is identical to that of TRBC1 gene [12]. The amino acid replacements were located, two in the N- terminus and one in the E β-strand and in the FG loop of well-defined regions of the extracellular domain of the TRBC molecule [15].…”

Section: Introductionmentioning

confidence: 99%

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Extensive analysis of D-J-C arrangements allows the identification of different mechanisms enhancing the diversity in sheep T cell receptor β-chain repertoire

et al. 2010

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BackgroundIn most species of mammals, the TRB locus has the common feature of a library of TRBV genes positioned at the 5'- end of two in tandem aligned D-J-C gene clusters, each composed of a single TRBD gene, 6-7 TRBJ genes and one TRBC gene. An enhancer located at the 3'end of the last TRBC and a well-defined promoter situated at the 5'end of the TRBD gene and/or a undefined promoter situated at the 5'end of the TRBD2 are sufficient to generate the full recombinase accessibility at the locus. In ruminant species, the 3'end of the TRB locus is characterized by the presence of three D-J-C clusters, each constituted by a single TRBD, 5-7 TRBJ and one TRBC genes with the center cluster showing a structure combined with the clusters upstream and downstream, suggesting that a unequal crossover occurred in the duplication. An enhancer downstream the last TRBC, and a promoter at the 5'-end of each TRBD gene are also present.ResultsIn this paper we focused our attention on the analysis of a large number of sheep TR β-chain transcripts derived from four different lymphoid tissues of three diverse sheep breed animals to certify the use and frequency of the three gene clusters in the β-chain repertoire. As the sheep TRB locus genomic organization is known, the exact interpretation of the V-D-J rearrangements was fully determined. Our results clearly demonstrate that sheep β-chain constitutes a level of variability that is substantially larger than that described in other mammalian species. This is due not only to the increase of the number of D and J genes available to the somatic recombination, but also to the presence of the trans-rearrangement process. Moreover, the functional complexity of β-chain repertoire is resolved by other mechanisms such as alternative cis- and trans-splicing and recombinational diversification that seems to affect the variety of the constant region.ConclusionAll together our data demonstrate that a disparate set of molecular mechanisms operate to perform a diversified repertoire in the sheep β-chain and this could confer some special biological properties to the corresponding αβ T cells in the ruminant lineage.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Extensive analysis of D-J-C arrangements allows the identification of different mechanisms enhancing the diversity in sheep T cell receptor β-chain repertoire

et al. 2010

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“…Porcine TRB harbours three functional D-J-C cluster units ); in contrast, human and mouse TRB has only two. An extensive TRD gene repertoire and duplication within the TRB locus have also been reported in other "γδ T cell high" species such as cattle (Conrad et al 2002;Connelley et al 2009;Herzig et al 2010) and sheep (Antonacci et al 2005(Antonacci et al , 2008. Studies of frequencies of translocations with breakpoints in TCR genes using whole chromosome painting probes in mice were performed on only a limited number of metaphases (Huang et al 2007;Bowen et al 2013).…”

Section: Discussionmentioning

confidence: 94%

Illegitimate recombination between T cell receptor genes in humans and pigs (Sus scrofa domestica)

et al. 2014

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T cell receptor (TCR) genes (TRA/TRD, TRB and TRG) reside in three regions on human chromosomes (14q11.2, 7q34 and 7p14, respectively) and pig chromosomes (7q15.3-q21, 18q11.3-q12 and 9q21-22, respectively). During the maturation of T cells, TCR genes are rearranged by site-specific recombination. Occasionally, interlocus recombination of different TCR genes takes place, resulting in chromosome rearrangements. It has been suggested that the absolute number of these "innocent" trans-rearrangements correlates with the risk of lymphoma. The aims of this work were to assess the frequencies of rearrangements with breakpoints in TCR genes in domestic pig lymphocytes and to compare these with the frequencies of corresponding rearrangements in human lymphocytes by using fluorescence in situ hybridization with chromosome painting probes. We show that frequencies of trans-rearrangements involving TRA/TRD locus in pigs are significantly higher than the frequency of translocations with breakpoints in TRB and TRG genes in pigs and the frequencies of corresponding trans-rearrangements involving TRA/TRD locus in humans. Complex structure of the pig TRA/TRD locus with high number of potential V(D)J rearrangements compared to the human locus may account for the observed differences. Furthermore, we demonstrated that trans-rearrangements involving pig TRA/TRD locus occur at lower frequencies in γδ T cells than in αβ T lymphocytes. The decrease of the frequencies in γδ T cells is probably caused by the absence of TRA recombination during maturation of this T cell lineage. High numbers of innocent trans-rearrangements in pigs may indicate a higher risk of T-cell lymphoma than in humans.

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Genomic characteristics of the T cell receptor (TRB) locus in the rabbit (Oryctolagus cuniculus) revealed by comparative and phylogenetic analyses

et al. 2014

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The present study identifies the genomic structure and the gene content of the T cell receptor beta (TRB) locus in the Oryctolagus cuniculus whole genome assembly. The rabbit locus spans less than 600 Kb and the general genomic organization is highly conserved with respect to other mammalian species. A pool of 74 TRB variable (TRBV) genes distributed in 24 subgroups are located upstream of two in tandem-aligned D-J-C gene clusters, each composed of one TRBD, six TRBJ genes, and one TRBC gene, followed by a single TRBV gene with an inverted transcriptional orientation. All TRB genes (functional, ORF, pseudogenes) of this paper have been approved by the IMGT/WHO-IUIS nomenclature committee. Additionally, five potentially functional protease serine (PRSS) trypsinogen or trypsinogen-like genes were identified: two in tandem PRSS-like genes, followed by two PRSS genes with unique traits, lie downstream of the TRBV1 gene and one PRSS gene is located about 400 Kb away downstream of the TRBV genes. Comparative and phylogenetic analyses revealed that multiple duplication events within a few subgroups have generated the germline repertoire of the rabbit TRBV genes, which is substantially larger than those described in humans, mice, and dogs, suggesting that a strong evolutionary pressure has selected the development of a species-specific TRBV repertoire. Hence, the genomic organization of the TRB locus in the genomes appears to be the result of a balance between the maintenance of a core-number of genes essential for the immunological performances and the requirement of newly arisen genes.

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Organization, structure and evolution of 41kb of genomic DNA spanning the D-J-C region of the sheep TRB locus

Cited by 23 publications

References 38 publications

Extensive analysis of D-J-C arrangements allows the identification of different mechanisms enhancing the diversity in sheep T cell receptor β-chain repertoire

Extensive analysis of D-J-C arrangements allows the identification of different mechanisms enhancing the diversity in sheep T cell receptor β-chain repertoire

Illegitimate recombination between T cell receptor genes in humans and pigs (Sus scrofa domestica)

Genomic characteristics of the T cell receptor (TRB) locus in the rabbit (Oryctolagus cuniculus) revealed by comparative and phylogenetic analyses

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