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墨西哥钝口螈T细胞抗原受体β链(TCRB)的DB和JB基因片段的结构、重排及个体发生表达

The structure, rearrangement, and ontogenic expression of DB and JB gene segments of the Mexican axolotl T-cell antigen receptor beta chain (TCRB).

作者信息

Kerfourn F, Charlemagne J, Fellah J S

机构信息

Université Pierre et Marie Curie and Centre National de la Recherche Scientifique, Groupe d'Immunologie Comparée, boite 29, 75252 Paris Cedex 05, France.

出版信息

Immunogenetics. 1996;44(4):275-85.

PMID:8753858
Abstract

We sequenced a total of 189 independent rearrangements in which the VB7.1 element is associated with CB1 (99 clones) or CB2 (90 clones) isotypes of the T-cell receptor (TCR) beta chain in the Mexican axolotl. Three stages of development were analyzed: 2.5 months, 10 months, and 25 months. Three JB1 segments were associated with the VB-CB1 rearrangements and six JB2 segments with VB-CB2. As in other vertebrates, some amino acid positions were conserved in all Jbetas (e. g., Phe-108, Gly-109, Gly-111, Thr-112, and Val-116). Two 11 nucleotides DB-like sequences, differed by one (A or T) central residue and could be productively read in the three putative reading frames. Most of the DB1 and JB1 segments were in the VB-CB1 clones, and most of the DB2 and JB2 segments were in the VB-CB2 clones, suggesting that the TCRB locus is organized into independent DB-JB-CB clusters that used the same collection of VB segments. About 40% of the beta-chain VDJ junctions in 2.5-month-old larvae had N nucleotides, compared with about 73% in 10 - 25-month old animals. The beta-chain VDJ junctions had about 30% of defective rearrangements at all stages of development, which could be due to the slow rate of cell division in the axolotl lymphoid organs, and the large genome in this urodele. Many of the axolotl CDRbeta3 sequences deduced for in frame VDJ rearrangements are the same in animals of different origins. Such redundancy could be a statistical effect due to the small number of thymocytes in the developing axolotl, rather than to some bias due to junctional preferences.

摘要

我们对总共189个独立重排进行了测序,其中在墨西哥钝口螈中,VB7.1元件与T细胞受体(TCR)β链的CB1(99个克隆)或CB2(90个克隆)同种型相关。分析了三个发育阶段:2.5个月、10个月和25个月。三个JB1片段与VB-CB1重排相关,六个JB2片段与VB-CB2重排相关。与其他脊椎动物一样,在所有Jβ中一些氨基酸位置是保守的(例如,苯丙氨酸-108、甘氨酸-109、甘氨酸-111、苏氨酸-112和缬氨酸-116)。两个11个核苷酸的DB样序列,在一个中心残基(A或T)上不同,并且可以在三个推定的阅读框中有效读取。大多数DB1和JB1片段在VB-CB1克隆中,大多数DB2和JB2片段在VB-CB2克隆中,这表明TCRB基因座被组织成独立的DB-JB-CB簇,这些簇使用相同的VB片段集合。在2.5个月大的幼虫中,约40%的β链VDJ连接有N核苷酸,而在10 - 25个月大的动物中约为73%。在发育的所有阶段,β链VDJ连接约有30%的重排存在缺陷,这可能是由于钝口螈淋巴器官中细胞分裂速度缓慢以及这种有尾两栖动物的基因组较大。从框架内VDJ重排推导的许多钝口螈CDRβ3序列在不同来源的动物中是相同的。这种冗余可能是由于发育中的钝口螈胸腺细胞数量较少导致的统计效应,而不是由于连接偏好引起的某些偏差。

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