# Control of CD8+ T cell migration and activation by Flightless-1

> **NIH NIH R21** · BENAROYA RESEARCH INST AT VIRGINIA MASON · 2021 · $261,150

## Abstract

PROJECT SUMMARY
Adaptive immune surveillance depends on the ability of T cells to successfully migrate through secondary
lymphoid tissues and form immune-synapses with antigen-presenting cells. Precise and dynamic organization
of the actin cytoskeleton is essential for both of these processes. In migrating T cells rapid reorganization of the
actin cytoskeleton is essential for cell polarization and chemotactic responses required for tissue entry and
proper micro-environmental positioning. During T cell activation, changes in the actin cytoskeleton control proper
formation of the immunological synapse, a highly organized cellular structure that allows T cells to properly
integrate signals from the T cell receptor with those from co-stimulatory molecules such as CD28 and integrins
such as LFA-1 (αLβ2). Flightless-1 (Flii) was initially identified in Drosophila as an actin modifying protein that
controls actin myofibril structure in the muscles that control flight. Flii contains an N-terminal leucine-rich repeat
(LRR) domain that facilitates protein-protein interaction and has been implicated in control of Ras activation of
Erk/Mapk signaling, Rac1 activation and PI3K signaling. The Flii C-terminus encodes 6 gelsolin-related domains
that can interact with actin and regulate actin filament assembly/disassembly. Based on its unique domain
structure, we hypothesize that Flii acts as a key regulator of CD8+ T cell homeostasis and function by linking
changes in the actin cytoskeleton during cell migration and activation with spatial control of various signaling
cascades. We will use state-of-the-art cellular and molecular techniques to study Flii function in physiologically
relevant and innovative mouse models. Completion of these studies will provide important new insights into a
novel and completely uncharacterized signaling hub that regulates CD8+ T cell-mediated immunity.

## Key facts

- **NIH application ID:** 10155177
- **Project number:** 1R21AI157440-01
- **Recipient organization:** BENAROYA RESEARCH INST AT VIRGINIA MASON
- **Principal Investigator:** Daniel J Campbell
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $261,150
- **Award type:** 1
- **Project period:** 2021-03-05 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10155177

## Citation

> US National Institutes of Health, RePORTER application 10155177, Control of CD8+ T cell migration and activation by Flightless-1 (1R21AI157440-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10155177. Licensed CC0.

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