Abstract
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.
Highlights
In most species of mammals, the T cell receptor beta (TRB) locus has the common feature of a library of T cell receptor beta variable gene (TRBV) genes positioned at the 5'- end of two in tandem aligned D-J-C gene clusters, each composed of a single T cell receptor beta diversity gene (TRBD) gene, 6-7 T cell receptor beta joining gene (TRBJ) genes and one T cell receptor beta constant gene (TRBC) gene
In 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, 6-7 TRBJ and one TRBC genes, followed by a single TRBV gene with an inverted transcriptional orientation located at the 3'-end
To know if the altered genomic architecture of the ruminant TRB locus can modify the mechanisms of recombination, we investigated on the β-chain repertoire in sheep
Summary
In 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. 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. The V(D)J process requires the binding of the lymphocytespecific recombination activating gene 1 and 2 (RAG1/2) protein complex to recombination signal sequences (RSs) flanking the rearranging sides of the individual V, D and J genes [1]. This phenomenon termed "beyond 12/23 rule" [4], preserving the TRBD gene utilization, ensures an ordered V(D)J recombination at the TRB locus with the TRBD-to-TRBJ joining which occurs before the TRBV-to-TRBD gene assembly
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