Evaluating the potential impact of mismatches outside the antigen recognition site in unrelated hematopoietic stem cell transplantation: HLA-DRB1*1454 and DRB1*140101
Evaluating the potential impact of mismatches outside the antigen recognition site in unrelated hematopoietic stem cell transplantation: HLA-DRB1*1454 and DRB1*140101
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DOI：
10.1111/j.1399-0039.2009.01245.x
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发表时间：
2009-06-01
期刊：
影响因子：
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通讯作者：
Hurley, C. K.
中科院分区：
文献类型：
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作者：
Xiao, Y.;Lazaro, A. M.;Hurley, C. K.
对来自4个美国人群的268个携带两个未解决的DRB1*14等位基因的个体进行DNA测序，发现DRB1*1454占大多数，这些等位基因仅在抗原识别位点外存在差异。查询4222对人白细胞抗原（HLA）匹配的造血干细胞移植供体-受体配对数据库，以确定DRB1*140101/DRB1*1454可能不匹配但I类位点匹配的数量。一项功率计算表明，在欧洲美国人中，需要超过88,000例移植才能确定足够的7/8等位基因匹配对，以评估DRB1*140101/DRB1*1454错配对移植结果的影响。HLA-DR与t细胞受体和CD4相互作用的分子模型表明，区分这两个等位基因的氨基酸替换对同种异体识别的影响最小。
DNA sequencing of 268 individuals drawn from four US populations carrying two unresolved DRB1*14 alleles differing only outside the antigen recognition site identified DRB1*1454 in the majority. A database of 4222 human leukocyte antigen (HLA)-matched hematopoietic stem cell transplantation donor-recipient pairs was queried to determine the number likely mismatched for DRB1*140101/DRB1*1454 but matched for class I loci. A power calculation suggests that more than 88,000 transplants among European Americans will be needed to identify sufficient 7/8 allele-matched pairs to evaluate the impact of the DRB1*140101/DRB1*1454 mismatch on transplant outcome. Molecular modeling of the HLA-DR interaction with the T-cell receptor and with CD4 suggests that the amino acid substitution distinguishing the two alleles will have minimal impact on allorecognition.