Scientists Pinpoint the Precise Mechanism That Decides the Fate of T Cells

A revealing study led by Hongbo Chi, Ph.D of St. Jude Children's Research Hospital in Memphis has isolated a protein complex that impacts the normal development of T cells. Mounting evidence shows that the metabolism plays a key role in the development of the immune system. However, this study established the exact protein complex that is responsible for regulating cell growth and metabolism, including influencing the developmental process of T cells. The name of the protein complex is mTORC1.

T cells can either develop conventionally or unconventionally. Researchers found that disrupting mTORC1 resulted in metabolic changes that would produce unconventional T cells. Scientists have long known that unconventional T cells and conventional T cells were different, as they express different cell surface receptors. Until this study, the precise mechanism that decided the fates of the T cells was unknown.

T cells use their unique receptors to recognize viruses and threats. A conventional T cell (αβ) has an alpha (α) protein chain and a beta (β) chain, and can be found in the spleen and lymph nodes. Unconventional T cells (γδ) are made from a gamma (γ) and a delta (δ) protein chain, and can be found in barrier tissues like the gut and skin.

Activating mTORC1 in animal models resulted in the upregulation of αβ (conventional) T cells. Conversely, disabling mTORC1 by deleting the RAPTOR protein resulted in the development of γδ (unconventional) T cells. Chi said "This research establishes mTORC1-driven metabolic signaling as a decisive factor in determining the fate of developing T cells and suggests metabolic processes are a fundamental mechanism that connects external signals with internal processes to guide the fate of immune cells".

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