# Modulating p56Lck in T-Cells by a Chimeric Peptide Comprising Two Functionally Different Motifs of Tip from Herpesvirus saimiri

## TL;DR

A chimeric peptide based on a viral protein can strongly boost T-cell proliferation and signaling, potentially leading to new therapeutic strategies.

## Contribution

The novel chimeric peptide hTip-CSKH was designed to target lipid rafts and modulate T-cell signaling and proliferation.

## Key findings

- hTip-CSKH induces a fivefold increase in T-cell proliferation in human and Aotus sp. cells.
- hTip-CSKH increases Lck phosphorylation and downstream signaling without requiring additional PKC stimulation.
- hTip-CSKH localizes to lipid rafts and inhibits Jurkat cells, indicating pathway-specific effects.

## Abstract

The Lck interacting protein Tip of Herpesvirus saimiri is responsible for T-cell transformation both in vitro and in vivo. Here we designed the chimeric peptide hTip-CSKH, comprising the Lck specific interacting motif CSKH of Tip and its hydrophobic transmembrane sequence (hTip), the latter as a vector targeting lipid rafts. We found that hTip-CSKH can induce a fivefold increase in proliferation of human and Aotus sp. T-cells. Costimulation with PMA did not enhance this proliferation rate, suggesting that hTip-CSKH is sufficient and independent of further PKC stimulation. We also found that human Lck phosphorylation was increased earlier after stimulation when T-cells were incubated previously with hTip-CSKH, supporting a strong signalling and proliferative effect of the chimeric peptide. Additionally, Lck downstream signalling was evident with hTip-CSKH but not with control peptides. Importantly, hTip-CSKH could be identified in heavy lipid rafts membrane fractions, a compartment where important T-cell signalling molecules (LAT, Ras, and Lck) are present during T-cell activation. Interestingly, hTip-CSKH was inhibitory to Jurkat cells, in total agreement with the different signalling pathways and activation requirements of this leukemic cell line. These results provide the basis for the development of new compounds capable of modulating therapeutic targets present in lipid rafts.