VIR576通过与TCR跨膜区结合抑制抗原特异性T细胞活化

VIR576 inhibits antigen-specific T cell activation by binding to the transmembrane domain of T cell receptor

目的探讨抗HIV多肽VIR576抑制抗原特异性T细胞活化的作用机制。方法OVA体外刺激分离的DO11.10小鼠抗原特异性T细胞,CCK-8法检测VIR576对其活化的影响。采用溶血试验、溶血抑制实验、荧光结合法等方法检测VIR576与TCR跨膜区序列(TCR-TMD)之间的相互作用。结果体外实验显示,VIR576能逆转HIVgp41融合多肽(FP)介导的抗原特异性T细胞活化,并且其自身也能抑制抗原特异性的T细胞活化(P<0.05)。溶血试验、溶血抑制实验、荧光结合法等方法证实,VIR576能与TCR-TMD特异性结合。结论VIR576对T细胞活化的作用是TCR依赖性的,通过与TCR-TMD结合抑制抗原特异性T细胞活化。VIR576兼具抑制HIV进入和抗原特异性T细胞活化的特性,可望作为预防HIV性传播的杀微生物剂进行研究。

Objective To study the mechanism underlying the inhibitory effect of the anti-HIV peptide VIR576 on antigen-specific T cell activation. Methods CCK-8 assay was used to investigate the effect of VIR576 on the proliferation of splenocytes of OVA-specific DO 11.10 Tg mice in response to chicken OVA. Hemolysis test, hemolysis inhibition assay and fluorescence binding assay were used to investigate the interaction of VIR576 with the transmembrane domain （TMD） of the T cell receptor （TCR）. Results VIR576 inhibited HIV glycoprotein gp41 fusion peptide-mediated antigen specific T cell activation, and VIR576 itself also inhibited splenocyte proliferation in responses to OVA （P〈0.05）. Hemolysis test, hemolysis inlubition assay and fluorescence binding assay demonstrated that VIR576 suppressed TCR-TMD-mediated hemolysis and competitively inhibited Rho-VIR576 binding to TCR-TMD peptide. Conclusion VIR576 is effective in suppressing the antigen-specific T cell activation via TCR and can interact with TCR-TMD. VIR576 may serve as a potent microbicide candidate to block sexual transmission of HIV due to of its inhibitory effect on both HIV entry and antigen-specific T cell activation.