Transfusion-related acute lung injury-associated HNA-3a antibodies recognize complex determinants on choline transporter-like protein 2.
Transfusion-related acute lung injury-associated HNA-3a antibodies recognize complex determinants on choline transporter-like protein 2.
复制标题
与输血相关的急性肺损伤相关的 HNA-3a 抗体可识别胆碱转运蛋白样蛋白 2 上的复杂决定因素。
DOI：
10.1111/trf.12717
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发表时间：
2014
期刊：
影响因子：
2.9
通讯作者：
Aster,RichardH
中科院分区：
文献类型：
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作者：
Bougie,DanielW;Peterson,JulieA;Kanack,AdamJ;Curtis,BrianR;Aster,RichardH
背景：当输血中存在HNA-3a特异性抗体时，可引起严重的，有时是致命的输血相关急性肺损伤（TRALI）。HNA3-a/b抗原是由在中性粒细胞、淋巴细胞和其他组织上表达的10膜胆碱转运蛋白样蛋白2 （CTL2）的五个细胞外环中的第一个中的R154Q多态性决定的。约50%的HNA-3a抗体（1型）可以使用含有R154的CTL2 Loop 1肽检测到；剩下的50%（2型）不能识别这个目标。了解这种差异的基础可以指导开发实用的检测方法来筛查献血者的HNA-3抗体。研究设计和方法采用流式细胞术和各种固相分析方法，研究了HNA-3a抗体对重组人、小鼠和人/小鼠（嵌合）CTL2的反应。结果表明，为了与CTL2结合，2型HNA-3a抗体需要CTL2细胞外环的第三个（可能是第二个）非多态性氨基酸残基处于与细胞膜中天然存在的结构相当的位置。相比之下，1型抗体只需要第一个细胞外环中含有R154的肽就可以识别。尽管使用含有R154的CTL2肽作为靶点的固相检测可以很容易地检测到1型HNA-3a抗体，但由于该抗体亚群识别的表位的复杂性，开发一种用于筛查献血者的2型抗体的实用测试将面临严峻的技术挑战。
Background HNA-3a specific antibodies can cause severe, sometimes fatal, transfusion related acute lung injury (TRALI) when present in transfused blood. The HNA3-a/b antigens are determined by an R154Q polymorphism in the first of five extracellular loops of the 10-membrane spanning choline transporter-like protein 2 (CTL2) expressed on neutrophils, lymphocytes and other tissues. About 50% of HNA-3a antibodies (Type 1) can be detected using CTL2 Loop 1 peptides containing R154; the remaining 50% (Type 2) fail to recognize this target. Understanding the basis for this difference could guide efforts to develop practical assays to screen blood donors for HNA-3 antibodies. Study design and methods Reactions of HNA-3a antibodies against recombinant versions of human, mouse, and human/mouse (chimeric) CTL2 were characterized using flow cytometry and various solid phase assays. Results Findings made show that, for binding to CTL2, Type 2 HNA-3a antibodies require non-polymorphic amino acid residues in the third, and possibly the second, extracellular loops of CTL2 to be in a configuration comparable to that found naturally in the cell membrane. In contrast, Type 1 antibodies require only peptides from the first extracellular loop that contain R154 for recognition. Conclusion Although Type 1 HNA-3a antibodies can readily be detected in solid phase assays that use a CTL2 peptide containing R154 as a target, development of a practical test to screen blood donors for Type 2 antibodies will pose a serious technical challenge because of the complex nature of the epitope(s) recognized by this antibody sub-group.