Kuwana Masataka
Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, 160-8582 Tokyo, Japan.
Autoimmun Rev. 2003 Jun;2(4):192-8. doi: 10.1016/s1568-9972(03)00007-7.
Antiphospholipid syndrome (APS) is characterized by recurrent thrombosis and intrauterine fetal loss in association with antiphospholipid antibodies (aPL). We have recently identified autoreactive CD4(+) T cells to beta(2)-glycoprotein I (beta(2)GPI) that promote aPL production in APS patients. beta(2)GPI-specific CD4(+) T cells preferentially recognize the antigenic peptide containing the major phospholipid-binding site in the context of DRB4*0103 (DR53). T-cell receptor beta chains of beta(2)GPI-specific T cells are highly restricted and mainly utilize rearranged Vbeta7 or Vbeta8 gene segments. T-cell helper activity that stimulates B cells to produce anti-beta(2)GPI antibodies is mediated through IL-6 and CD40-CD40 ligand engagement. beta(2)GPI-specific T cells respond to reduced beta(2)GPI and recombinant beta(2)GPI fragments produced in bacteria, but not to native beta(2)GPI, indicating that the epitopes recognized by beta(2)GPI-specific T cells are apparently cryptic. Activation of beta(2)GPI-specific T cells resulting in production of pathogenic anti-beta(2)GPI antibodies can be induced by the exposure to cryptic peptides of beta(2)GPI. Finally, beta(2)GPI-specific T cell is a reasonable target of potential therapeutic strategies that selectively suppress pathogenic aPL production in APS patients.
抗磷脂综合征（APS）的特征是反复出现血栓形成和与抗磷脂抗体（aPL）相关的宫内胎儿丢失。我们最近在APS患者中发现了针对β2糖蛋白I（β2GPI）的自身反应性CD4+ T细胞，这些细胞可促进aPL的产生。β2GPI特异性CD4+ T细胞在DRB4*0103（DR53）背景下优先识别含有主要磷脂结合位点的抗原肽。β2GPI特异性T细胞的T细胞受体β链高度受限，主要利用重排的Vβ7或Vβ8基因片段。刺激B细胞产生抗β2GPI抗体的T细胞辅助活性是通过IL-6和CD40-CD40配体相互作用介导的。β2GPI特异性T细胞对细菌产生的减少的β2GPI和重组β2GPI片段有反应，但对天然β2GPI没有反应，这表明β2GPI特异性T细胞识别的表位显然是隐蔽的。暴露于β2GPI的隐蔽肽可诱导β2GPI特异性T细胞活化，从而导致致病性抗β2GPI抗体的产生。最后，β2GPI特异性T细胞是选择性抑制APS患者致病性aPL产生的潜在治疗策略的合理靶点。
