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A simple electronic tool for assessing amino acid sequence polymorphisms within exon-2 of HLA-DPB1 alleles.
Human Immunology ( IF 2.7 ) Pub Date : 2020-07-16 , DOI: 10.1016/j.humimm.2020.06.011
H Clifford Sullivan 1 , Loren Gragert 2 , Geoffrey H Smith 3 , Kelsi Lindblad 3 , Howard M Gebel 1 , Robert A Bray 1
Affiliation  

In November 2014, the OPTN/UNOS Board of Directors mandated that HLA-DPB1 typing be performed for all deceased donors. Currently, there are over 1,000 known HLA DPB1 alleles, yet fewer than 30 are represented on commonly used single antigen bead (SAB) solid phase antibody assays. Moreover, the official World Health Organization (WHO) nomenclature for the DPB1 locus does not permit assessment of structural relationships between alleles based on their names. Thus, for donor DPB1 alleles lacking a corresponding SAB, determining the compatibility between a donor-recipient pair when the recipient possesses DPB1 antibodies currently requires the use of manual sequence alignments. Multiple studies have reported that DPB1 alleles can be classified into serological-defined categories based on shared protein sequence motifs residing in distinct hypervariable regions. To date, six such motifs have been recognized. To address this problem, we developed a computer-assisted tool to compare donor and recipient DPB1 allele sequences, specifically those defined by DPB1 hypervariable region motifs located in exon 2 (http://dpreport.hlatools.org). This tool quickly identifies mismatched DPB1 motifs, and easily permits the identification of motif-based donor-specific antibodies (DSA) to DPB1.



中文翻译:

一个简单的电子工具,用于评估HLA-DPB1等位基因外显子2内的氨基酸序列多态性。

2014年11月,OPTN / UNOS董事会要求对所有死者进行HLA-DPB1打字。当前,已知HLA DPB1等位基因超过1,000个,但在常用的单抗原珠(SAB)固相抗体测定中仅代表不到30个。此外,DPB1基因座的官方世界卫生组织(WHO)命名法不允许根据等位基因的名称评估等位基因之间的结构关系。因此,对于缺乏相应SAB的供体DPB1等位基因,当受体拥有DPB1抗体时,确定供体-受体对之间的兼容性目前需要使用手动序列比对。多项研究报告称,DPB1等位基因可以基于存在于不同高变区内的共享蛋白序列基序,分为血清学定义的类别。迄今为止,已经识别出六个这样的图案。为了解决这个问题,我们开发了一种计算机辅助工具来比较供体和受体DPB1等位基因序列,特别是由位于第2外显子上的DPB1高变区基序定义的序列(http://dpreport.hlatools.org 。该工具可以快速识别不匹配的DPB1主题,并轻松允许识别针对DPB1的基于主题的供体特异性抗体(DSA)。

更新日期:2020-08-15
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