Antibody complementarity-determining regions (CDRs): a bridge between adaptive and innate immunity.
Antibody complementarity-determining regions (CDRs): a bridge between adaptive and innate immunity.
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DOI：
10.1371/journal.pone.0008187
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发表时间：
2009-12-04
期刊：
影响因子：
3.7
通讯作者：
Polonelli L
中科院分区：
文献类型：
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作者：
Gabrielli E;Pericolini E;Cenci E;Ortelli F;Magliani W;Ciociola T;Bistoni F;Conti S;Vecchiarelli A;Polonelli L
已经证明，独立于天然抗体（Ab）对给定抗原（Ag）的特异性，互补决定区（CDR）相关肽可以显示不同的抗微生物、抗病毒和抗肿瘤活性。在这项研究中，我们证明了与对二岩藻糖基人血型A特异性的小鼠单克隆抗体（mAb）的VHCDR 3序列相同的合成肽容易被巨噬细胞摄取，随后刺激：i）促炎细胞因子产生; ii）PI 3 K-Akt途径和iii）TLR-4表达。值得注意的是，VHCDR 3对系统性念珠菌病发挥治疗作用，而不具有直接的杀念珠菌特性。这些结果开辟了一种新的可能性，即在免疫球蛋白的半衰期之外，抗体片段可能会以一种让人想起先天免疫调节肽的方式有效地影响抗感染细胞免疫反应。
It has been documented that, independently from the specificity of the native antibody (Ab) for a given antigen (Ag), complementarity determining regions (CDR)-related peptides may display differential antimicrobial, antiviral and antitumor activities. In this study we demonstrate that a synthetic peptide with sequence identical to VHCDR3 of a mouse monoclonal Ab (mAb) specific for difucosyl human blood group A is easily taken up by macrophages with subsequent stimulation of: i) proinflammatory cytokine production; ii) PI3K-Akt pathway and iii) TLR-4 expression. Significantly, VHCDR3 exerts therapeutic effect against systemic candidiasis without possessing direct candidacidal properties. These results open a new scenario about the possibility that, beyond the half life of immunoglobulins, Ab fragments may effectively influence the antiinfective cellular immune response in a way reminiscent of regulatory peptides of innate immunity.