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2018 ; 8
(1
): 9747
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Gp41 dynamically interacts with the TCR in the immune synapse and promotes early
T cell activation
#MMPMID29950577
Yakovian O
; Schwarzer R
; Sajman J
; Neve-Oz Y
; Razvag Y
; Herrmann A
; Sherman E
Sci Rep
2018[Jun]; 8
(1
): 9747
PMID29950577
show ga
The HIV-1 glycoprotein gp41 critically mediates CD4(+) T-cell infection by HIV-1
during viral entry, assembly, and release. Although multiple immune-regulatory
activities of gp41 have been reported, the underlying mechanisms of these
activities remain poorly understood. Here we employed multi-colour single
molecule localization microscopy (SMLM) to resolve interactions of gp41 proteins
with cellular proteins at the plasma membrane (PM) of fixed and live CD4(+)
T-cells with resolution of ~20-30?nm. We observed that gp41 clusters dynamically
associated with the T cell antigen receptor (TCR) at the immune synapse upon TCR
stimulation. This interaction, confirmed by FRET, depended on the virus clone,
was reduced by the gp41 ectodomain in tight contacts, and was completely
abrogated by mutation of the gp41 transmembrane domain. Strikingly, gp41
preferentially colocalized with phosphorylated TCRs at the PM of activated
T-cells and promoted TCR phosphorylation. Gp41 expression also resulted in
enhanced CD69 upregulation, and in massive cell death after 24-48?hrs. Our
results shed new light on HIV-1 assembly mechanisms at the PM of host T-cells and
its impact on TCR stimulation.
|Cell Line
[MESH]
|HIV Envelope Protein gp41/genetics/*metabolism
[MESH]