The anti-non-gal xenoantibody response to xenoantigens on gal knockout pig cells is encoded by a restricted number of germline progenitors.
The anti-non-gal xenoantibody response to xenoantigens on gal knockout pig cells is encoded by a restricted number of germline progenitors.
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DOI：
10.1111/j.1600-6143.2008.02337.x
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发表时间：
2008-09
期刊：
影响因子：
--
通讯作者：
Kearns-Jonker M
中科院分区：
文献类型：
--
作者：
Kiernan K;Harnden I;Gunthart M;Gregory C;Meisner J;Kearns-Jonker M
当gal敲除（GalTKO）猪器官移植到非人灵长类动物时，针对非半乳糖异种抗原的抗体负责急性体液异种移植排斥反应。我们利用恒河猴的外周血淋巴细胞在免疫GalTKO猪内皮细胞后产生活跃的异种抗体反应，生成了IgM和IgG基因文库，并利用这些文库鉴定了编码对非gal猪异种抗原产生抗体反应的IgVH基因。源自IGHV3-21种系祖细胞的免疫球蛋白基因编码针对非半乳糖异种抗原的异种抗体。用表达半乳糖糖的α1,3半乳糖转移酶基因的慢病毒载体转导GalTKO细胞，导致“抗非半乳糖”异种抗体与表达半乳糖糖的转导GalTKO细胞的高水平结合，表明抗非半乳糖异种抗体与碳水化合物异种抗原发生交叉反应。编码iGb3合成酶的半乳糖转移酶2基因在GalTKO猪细胞中不表达。我们的研究结果表明，灵长类动物的抗非半乳糖异种抗体是由IgVH基因编码的，该基因局限于IGHV3-21，并结合到与半乳糖碳水化合物结构相关但不同的表位上。
Antibodies directed at non-gal xenoantigens are responsible for acute humoral xenograft rejection when gal knockout (GalTKO) pig organs are transplanted into non-human primates. We generated IgM and IgG gene libraries using peripheral blood lymphocytes of rhesus monkeys initiating active xenoantibody responses after immunization with GalTKO pig endothelial cells and used these libraries to identify IgVH genes that encode antibody responses to non-gal pig xenoantigens. Immunoglobulin genes derived from the IGHV3-21 germline progenitor encode xenoantibodies directed at non-gal xenoantigens. Transduction of GalTKO cells with lentiviral vectors expressing the porcine α1,3 galactosyltransferase gene responsible for gal carbohydrate expression results in a higher level of binding of “anti-non-gal” xenoantibodies to transduced GalTKO cells expressing the gal carbohydrate, suggesting that anti-non-gal xenoantibodies crossreact with carbohydrate xenoantigens. The galactosyltransferase 2 gene encoding isoglobotriaosylceramide synthase (iGb3 synthase) is not expressed in GalTKO pig cells. Our results demonstrate that anti-non-gal xenoantibodies in primates are encoded by IgVH genes that are restricted to IGHV3-21 and bind to an epitope that is structurally related to but distinct from the Gal carbohydrate.
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影响因子：
5.1
作者：
Fischer-Lougheed, J. Y.;Tarantal, A. F.;Kearns-Jonker, M.
通讯作者：
Kearns-Jonker, M.
影响因子：
3.2
作者：
Bible, JM;Howard, W;Dunn-Walters, DK
通讯作者：
Dunn-Walters, DK
影响因子：
4
作者：
Milland, Julie;Yuriev, Elizabeth;Sandrin, Mauro S.
通讯作者：
Sandrin, Mauro S.
影响因子：
56.9
作者：
Lai, LX;Kolber-Simonds, D;Prather, RS
通讯作者：
Prather, RS
DOI：
10.1038/nsb1014
发表时间：
2003-12-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Nguyen, HP;Seto, NOL;Evans, SV
通讯作者：
Evans, SV