Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Universita' del Salento, Lecce, Italy.
BMC Genomics. 2010 Jan 4;11:3. doi: 10.1186/1471-2164-11-3.
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. 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.
In this paper we focused our attention on the analysis of a large number of sheep TR beta-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 beta-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 beta-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 beta-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.
All together our data demonstrate that a disparate set of molecular mechanisms operate to perform a diversified repertoire in the sheep beta-chain and this could confer some special biological properties to the corresponding alphabeta T cells in the ruminant lineage.
在大多数哺乳动物物种中，TRB 基因座具有一个共同的特征，即位于两个串联排列的 D-J-C 基因簇 5'端的 TRBV 基因文库，每个基因簇由单个 TRBD 基因、6-7 个 TRBJ 基因和一个 TRBC 基因组成。位于最后一个 TRBC 基因 3'端的增强子和位于 TRBD 基因 5'端的明确启动子或位于 TRBD2 基因 5'端的未定义启动子足以在基因座上产生完全的重组酶可及性。在反刍动物物种中，TRB 基因座的 3'端的特征是存在三个 D-J-C 基因簇，每个基因簇由单个 TRBD、5-7 个 TRBJ 和一个 TRBC 基因组成，中心基因簇的结构与上下游基因簇结合，表明在复制过程中发生了不等交换。最后一个 TRBC 基因下游也存在一个增强子，以及每个 TRBD 基因 5'端的一个启动子。
在本文中，我们将注意力集中在分析来自三个不同绵羊品种的四个不同淋巴组织的大量绵羊 TRβ 链转录本上，以证明三个基因簇在β链库中的使用和频率。由于已知绵羊 TRB 基因座基因组组织，因此可以完全确定 V-D-J 重排的准确解释。我们的结果清楚地表明，绵羊β链构成的变异性水平远大于其他哺乳动物物种描述的水平。这不仅是由于体细胞重组可用的 D 和 J 基因数量增加，还由于存在跨重排过程。此外，β链库的功能复杂性通过其他机制得到解决，例如替代性顺式和反式剪接和重组多样化，这似乎影响了恒定区的多样性。
总之，我们的数据表明，一组不同的分子机制在绵羊β链中发挥作用，以执行多样化的库，这可能赋予反刍动物谱系中相应的αβ T 细胞一些特殊的生物学特性。
