β2-glycoprotein I:: antiphospholipid syndrome and T-cell reactivity
β2-glycoprotein I:: antiphospholipid syndrome and T-cell reactivity
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DOI：
10.1016/j.thromres.2004.06.029
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发表时间：
2004-01-01
影响因子：
7.5
通讯作者：
Kuwana, M
中科院分区：
文献类型：
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作者：
Kuwana, M
越来越多的证据表明，抗磷脂抗体（aPL）可导致抗磷脂综合征（APS）反复血栓形成和宫内流产。我们最近发现了自身反应性CD 4（+）T细胞对β 2-糖蛋白I（β 2 GPI）的反应，这种反应可促进致病性抗磷脂抗体的产生。β（2）GPI特异性CD 4（+）T细胞优先识别DR 53中含有主要磷脂（PL）结合位点的抗原肽。刺激B细胞产生IgG抗β（2）GPI抗体的T细胞辅助活性通过IL-6和CD 40-CD 154相互作用介导。β（2）GPI特异性T细胞对细菌表达系统中产生的还原的β（2）GPI和重组的β（2）GPI片段有应答，但对天然的β（2）GPI无应答，表明β（2）GPI特异性T细胞识别的表位是“隐蔽的”决定簇，其在正常情况下通过加工天然的β（2）GPI以亚阈值水平产生。尽管在APS患者和健康个体中都检测到β（2）GPI特异性T细胞，但这些自身反应性T细胞在APS患者体内被激活，而在健康个体中则没有。这些发现表明β（2）GPI特异性T细胞的活化和随后致病性抗β（2）GPI抗体的产生可以通过将此类T细胞暴露于由功能性抗原呈递细胞（APC）有效呈递的β（2）GPI的隐蔽肽来诱导。描述诱导有效加工和呈递β（2）GPI的隐蔽决定簇作为抗原加工的结果的机制，将阐明引发APS中自身抗体应答的病因。(c)2004 Elsevier Ltd.保留所有权利。
There is increasing evidence showing that recurrent thrombosis and intrauterine fetal loss in anti phospholipid syndrome (APS) are attributable to antiphosphotipid (aPL) antibodies. We have recently identified autoreactive CD4(+) T cells to beta(2)-glycoprotein I (beta(2)GPI) that promote production of pathogenic antiphosphotipid antibodies. beta(2)GPI-specific CD4(+) T cells preferentially recognize the antigenic peptide containing the major phospholipid (PL)-binding site in the context of DR53. T-cell helper activity that stimulates B cells to produce IgG anti-beta(2)GPI antibodies is mediated through IL-6 and CD40-CD154 interaction. beta(2)GPI-specific T cells respond to reduced beta(2)GPI and recombinant beta(2)GPI fragments produced in a bacterial expression system but not to native beta(2)GPI, indicating that the epitopes recognized by beta(2)GPI-specific T cells are 'cryptic' determinants, which are generated at a subthreshold level by the processing of native beta(2)GPI under normal circumstances. Although beta(2)GPI-specific T cells are detected in both APS patients and healthy individuals, these autoreactive T cells are activated in vivo in APS patients but not in healthy individuals. These findings indicate activation of beta(2)GPI-specific T cells and subsequent production of pathogenic anti-beta(2)GPI antibodies can be induced by the exposure of such T cells to cryptic peptides of beta(2)GPI efficiently presented by functional antigen-presenting cells (APC). Delineating the mechanisms that induce the efficient processing and presentation of cryptic determinants of beta(2)GPI as a consequence of antigen processing would clarify the etiology that initiates the autoantibody response in APS. (c) 2004 Elsevier Ltd. All rights reserved.