Sequence and diversity of T-cell receptor β-chain V and J genes of the owl monkey Aotus nancymaae
Sequence and diversity of T-cell receptor β-chain V and J genes of the owl monkey Aotus nancymaae
复制标题
鸮猴Aotus nancymaae T细胞受体β链V和J基因的序列和多样性
作者：
W. Vecino;C. Daubenberger;R. Rodríguez;A. Moreno;M. Patarroyo;G. Pluschke
摘要新大陆灵长类动物南猿Aotus nancymaae易感染人类恶性疟原虫，因此被世界卫生组织推荐作为评估疟疾疫苗候选物的模型。 最近，我们已经表明，Aotus TCRVA基因和TCRJA片段表现出高度的相似性，以人类同行。本研究采用逆转录聚合酶链反应技术对A. nancymaaeTCRβ链基因重排。与人类序列比对和系统发育比较鉴定了18个不同的AotusTCRBV基因，其与人类TCRBV基因家族2、4、5、6、7、9、12、15、24和28同源。在TCRBV 4、5、6和7家族中发现了多个Aotus基因。这些TCRBV基因中的一些与相同的人类基因最佳对齐，因此似乎没有单独的人类同源物。AotusTCRBV基因的氨基酸序列与其最接近的人类对应物具有77%至90%的相同性。结果表明，Aotus TCRBJ基因有10个片段与人TCRBJ基因片段J1-1、J1-2、J1-4、J1-5、J1-6、J2-1、J2-2、J2-3、J2-4、J2-5同源，有些片段的氨基酸序列与人TCRBJ基因片段完全相同。Aotus与人β链编码基因中同义和非同义取代比例的比较显示TCRBJ区段中同义取代和TCRBV区段中非同义取代占优势。TCRBV CDR 1和CDR 2区的非同义取代的优势比框架区更明显。没有证据表明出现新的TCRBJ片段或TCRBV家族，这些结果证实了灵长类动物的TCR库是非常稳定的，并支持使用Aotus猴作为感染模型的概念，用于评估未来的亚单位疫苗候选人。
Abstract The New World primate Aotus nancymaae is susceptible to infection with the human malaria parasite Plasmodium falciparum and has therefore been recommended by the World Health Organization as a model for the evaluation of malaria vaccine candidates. Recently, we have shown that Aotus TCRVA genes and TCRJA segments exhibit a high degree of similarity to human counterparts. In the present report we used reverse transcription polymerase chain reaction to analyze the sequences of A. nancymaaeTCRβ-chain gene rearrangements. Alignment with human sequences and phylogenetic comparison identified 18 distinct AotusTCRBV genes homologous to the human TCRBV gene families 2, 4, 5, 6, 7, 9, 12, 15, 24, and 28. Multiple Aotus genes were found in the TCRBV4, 5, 6, and 7 families. Some of these TCRBV genes aligned best to the same human gene and thus do not seem to have separate human homologues. Amino acid sequences of the AotusTCRBV genes were 77 to 90% identical to their closest human counterparts. Ten distinct AotusTCRBJ segments homologous to the human segments J1-1, J1-2, J1-4, J1-5, J1-6, J2-1, J2-2, J2-3, J2-4, J2-5 were found. In some cases the amino acid sequences of Aotus and human TCRBJ segments were completely identical. A comparison of the proportion of synonymous and non-synonymous substitutions in Aotus vs human β-chain-encoding genes revealed a dominance of synonymous substitutions in TCRBJ segments and of nonsynonymous substitutions in TCRBV segments. Dominance of nonsynonymous substitutions was more pronounced in TCRBV CDR1 and CDR2 regions than in the framework regions. No evidence for the emergence of new TCRBJ segments or TCRBV families was found. These results confirm that the TCR repertoire in primates is remarkably stable and support the concept of using Aotus monkeys as an infection model for the evaluation of future subunit vaccine candidates.
DOI：
10.1073/pnas.86.23.9253
发表时间：
1989-12-01
影响因子：
11.1
作者：
KEOHAVONG, P;THILLY, WG
通讯作者：
THILLY, WG