Regulation of primary alloantibody response through antecedent exposure to a microbial T-cell epitope
Regulation of primary alloantibody response through antecedent exposure to a microbial T-cell epitope
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DOI：
10.1182/blood-2009-08-238568
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发表时间：
2010-05-13
期刊：
影响因子：
20.3
通讯作者：
Zimring, James C.
中科院分区：
文献类型：
--
作者：
Hudson, Krystalyn E.;Lin, Eugene;Zimring, James C.
红细胞(RBC)抗原的体液免疫是一个临床上重要的问题，它可能导致输血反应和寻找未来相容的输血的困难。然而，人们对调节应答者/无应答者状态的因素只有部分了解。在这里，我们鉴定了一系列含有Kell、Kidd和Duffy抗原变异氨基酸的8-9氨基酸多肽中100%同源性的微生物。为了验证这种微生物感染易导致红细胞同种异体免疫的假设，建立了一种小鼠多瘤病毒，该病毒表达一个定义的CD4(+)T细胞表位卵清蛋白(323-339)((OVA)(323-339))，然后与表达B细胞表位的红细胞(鸡蛋溶菌酶[HEL])融合到(OVA)(323-339)中输注。虽然单独感染没有诱导出可检测到的抗-HEL，但随后的红细胞输注在先前感染的小鼠中诱导了100-1000倍的抗-HEL。野生型多瘤病毒或单独表达HEL的红细胞不会产生这种效应。总之，这些数据表明，事先接触与RBC抗原具有小肽同源性的病原体可以导致增强的初级同种异体抗体反应。由于目前的临床测试无法检测到这种启动，目前尚不清楚这种情况在人类同种异体免疫中发生的程度。(血。2010；115(19)：3989-3996)
Humoral alloimmunization to red blood cell (RBC) antigens is a clinically significant problem that can lead to transfusion reactions and difficulty in locating future compatible blood for transfusion. However, factors regulating responder/nonresponder status are only partially understood. Herein, we identify a series of microbes with 100% identity in 8- to 9-amino acid peptides containing the variant amino acids in Kell, Kidd, and Duffy antigens. To test the hypothesis that infection with such a microbe could predispose to RBC alloimmunization, a mouse model was developed using murine polyoma virus expressing a defined CD4(+) T-cell epitope ovalbumin(323-339) ((OVA)(323-339)) and subsequent transfusion with RBCs expressing a B-cell epitope (hen egg lysozyme [HEL]) fused to (OVA)(323-339). Whereas infection alone induced no detectable anti-HEL, subsequent RBC transfusion induced 100- to 1000-fold more anti-HEL in mice that had been previously infected compared with control mice. This effect did not occur with wild-type polyoma virus or RBCs expressing HEL alone. Together, these data indicate that prior exposure to a pathogen with small peptide homology to RBC antigens can lead to an enhanced primary alloantibody response. As such priming is not detectable by current clinical tests, it is unknown to what extent this occurs in human alloimmunization. (Blood. 2010; 115(19): 3989-3996)