DIVERGENT EVOLUTION OF T-CELL REPERTOIRES - EXTENSIVE DIVERSITY AND DEVELOPMENTALLY REGULATED EXPRESSION OF THE SHEEP GAMMA-DELTA T-CELL RECEPTOR

DIVERGENT EVOLUTION OF T-CELL REPERTOIRES - EXTENSIVE DIVERSITY AND DEVELOPMENTALLY REGULATED EXPRESSION OF THE SHEEP GAMMA-DELTA T-CELL RECEPTOR
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DOI:
10.1002/j.1460-2075.1993.tb05705.x
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发表时间:
1993-02-01
期刊:
影响因子:
11.4
通讯作者:
DUDLER, L
DUDLER, L
中科院分区:
生物学1区
文献类型:
--
作者:
HEIN, WR;DUDLER, L

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绵羊 gammadelta T 细胞表达前所未有的抗原受体库,这是由于可变区和恒定区基因片段多样性的增加所致。可变区多样性主要源于重复Vdelta基因大家族的利用,这些基因保留了两个不同的高变片段,与其他抗原受体V基因中存在的互补决定区相当。这意味着绵羊 Vdelta 链在进化过程中经过了严格的选择,可能是在涉及配体识别的位点。羊γδ异二聚体存在于至少五种同种型变体中,这些变体是由单个Cδ片段与五个功能性Cγ片段之一结合形成的,每个片段都具有独特的铰链区。我们的分析还表明,正常外周系统的建立既受发育调节,又依赖于个体发育过程中功能性胸腺的持续存在。扩展的 V 基因库和多种受体同种型的存在,以及羊免疫系统中 γδ T 细胞的突出地位,表明这种 T 细胞谱系在这一进化途径中具有更复杂的功能作用。
Sheep gammadelta T cells express an unprecedented repertoire of antigen receptors contributed by increased diversity in both variable and constant region gene segments. Variable region diversity results mainly from the utilization of a large family of duplicated Vdelta genes that have retained two distinct hypervariable segments comparable with the complementarity determining regions present in other antigen receptor V genes. This implies that sheep Vdelta chains have been intensely selected during evolution, probably at sites involved in ligand recognition. The sheep gammadelta heterodimer occurs in at least five isotypic variants formed by the association of a single Cdelta segment with one of five functional Cgamma segments, each with distinctive hinge regions. Our analysis also shows that the establishment of a normal peripheral repertoire is both developmentally regulated and dependent on the continual presence of a functional thymus during ontogeny. The existence of an expanded V gene repertoire and multiple receptor isotypes together with the prominence of gammadelta T cells in the sheep immune system argues that this lineage of T cells has a more elaborate functional role in this evolutionary pathway.