Baboon immunoglobulin constant region heavy chains:: identification of four IGHG genes

Baboon immunoglobulin constant region heavy chains:: identification of four IGHG genes
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DOI:
10.1007/s00251-002-0505-1
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发表时间:
2002-11-01
期刊:
影响因子:
3.2
通讯作者:
Scinicariello, F
Scinicariello, F
中科院分区:
医学4区
文献类型:
--
作者:
Attanasio, R;Jayashankar, L;Scinicariello, F

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非人灵长类动物模型在生物医学研究,特别是在疫苗开发中的应用越来越多,这就要求对它们的免疫球蛋白基因和相应产物进行表征。因此,我们测序,克隆和特点的四个免疫球蛋白γ链恒定区基因(IGHG)存在于狒狒。基于与编码IgG1、IgG2、IgG3和IgG4亚类的四种人基因和三种已知恒河猴IGHG基因的序列相似性,将这四种基因命名为IGHG 1、IGHG 2、IGHG 3和IGHG 4。具体而言,狒狒IgG1、IgG2、IgG3和IgG4序列与其人对应物具有90.3%、88.3%、86.7%和89.6%的氨基酸同一性。狒狒IgG 1、IgG 2和IgG 3与相应的恒河猴序列的氨基酸同源性百分比分别为98.5%、93.1%和94.4%。因此,狒狒和恒河猴IGHG基因高度同源。狒狒和人类序列之间存在的大多数差异集中在铰链区,其中上铰链是最多样化的,含有几个脯氨酸残基。与恒河猴相似,所有狒狒IGHG基因的铰链区由单个外显子组成,而在人类中,IgG 3分子由多个外显子编码。这些结果证实了铰链区的进化不稳定性,并表明与狒狒和人IgG分子的铰链区相关的功能特性可能在两个物种之间存在差异。
The increasing use of nonhuman primate models in biomedical research and especially in vaccine development requires the characterization of their immunoglobulin genes and corresponding products. Therefore, we sequenced, cloned and characterized the four immunoglobulin gamma chain constant region genes (IGHG) present in baboons. These four genes were designated IGHG1, IGHG2, IGHG3 and IGHG4 on the basis of sequence similarities with the four human genes encoding the IgG1, IgG2, IgG3 and IgG4 subclasses and the three known rhesus macaque IGHG genes. Specifically, the baboon IgG1, IgG2, IgG3 and IgG4 sequences exhibit 90.3%, 88.3%, 86.7% and 89.6% amino acid identity to their human counterpart. The percent of amino acid identity of baboon IgG1, IgG2 and IgG3 to the corresponding rhesus macaque sequences is 98.5, 93.1 and 94.4, respectively. Therefore, baboon and rhesus macaque IGHG genes are highly homologous to each other. The majority of differences existing between baboon and human sequences are clustered in the hinge region, with the upper hinge being the most diverse and containing several proline residues. Similar to rhesus macaques, the hinge regions of all baboon IGHG genes consist of a single exon, whereas in humans the IgG3 molecule is encoded by multiple exons. These results confirm the evolutionary instability of the hinge region and indicate that functional properties associated with the hinge regions of baboon and human IgG molecules might differ between the two species.