[VIR576 inhibits antigen-specific T cell activation by binding to the transmembrane domain of T cell receptor].
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 DO11.10 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 inhibition assay and fluorescence binding assay demonstrated that VIR576 suppressed TCR-TMD-mediated hemolysis and competitively inhibited Rho-VIR576 binding to TCR-TMD peptide.


CONCLUSIONS
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.
Zhang
Rui-tao
RT
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. zrt0116@126.com
Li
Xiao-juan
XJ
Li
Run-ming
RM
Hu
Yi-ping
YP
Jiang
Shi-bo
SB
Liu
Shu-wen
SW
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D015658:HIV Infections / Q000517:prevention & control; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D053586:Virus Internalization / Q000187:drug effects
D019380:Anti-HIV Agents; D011948:Receptors, Antigen, T-Cell