Intercellular transfer of oncogenic H-Ras at the immunological synapse

Oded Rechavi, Itamar Goldstein, Helly Vernitsky, Barak Rotblat, Yoel Kloog

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Immune cells establish dynamic adhesive cell-cell interactions at a specific contact region, termed the immunological synapse (IS). Intriguing features of the IS are the formation of regions of plasma membrane fusion and the intercellular. exchange of membrane fragments between the conjugated cells. it is not known whether upon IS formation, intact intracellular proteins can transfer from target cells to lymphocytes to allow the transmission of signals across cell boundaries. Here we show by both FACS and confocal microscopy that human lymphocytes acquire from the cells they scan the inner-membrane protein H-Ras, a G-protein vital for common lymphocyte functions and a prominent participant in human cancer. The transfer was cell contact-dependent and occurred in the context of cell-conjugate formation. Moreover, the acquisition of oncogenic H-RasG12V by natural killer (NK) and T lymphocytes had important biological functions in the adopting lymphocytes: the transferred H- RasG12V induced ERK phosphorylation, increased interferon-γ and tumor necrosis factor-α secretion, enhanced lymphocyte proliferation, and augmented NK-mediated target cell killing. Our findings reveal a novel mode of cell-to-cell communication - allowing lymphocytes to extend the confines of their own proteome - which may moreover play an important role in natural tumor immunity.

Original languageEnglish
Article numbere1204
JournalPLoS ONE
Volume2
Issue number11
DOIs
StatePublished - 21 Nov 2007
Externally publishedYes

ASJC Scopus subject areas

  • General

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