January 26, 2015

Immune response depends on force

New studies explain how T-cell receptors use force to recognize and protect us against pathogens.

White blood cells in the bloodstream. (iStock)

Recognition of rare “foreign” peptides by the alpha-beta T-cell receptor (TCR) on T lymphocytes is critical for the adaptive immune response that protects our bodies. T cell motions during immune surveillance generate forces that are detected by the mechanosensing action of the TCR.

Using single-molecule and single-cell optical tweezer assays, Matthew Lang, Ph.D., and colleagues at Vanderbilt and at the Dana-Farber Cancer Institute in Boston demonstrate that the TCR uses force to enhance binding to foreign peptides and transitions to an extended conformation to release. They found that another part of the TCR complex controls the bond strength and extension transition in this “catch-and-release” model for TCR function.

The findings, reported this week in the Proceedings of the National Academy of Sciences, explain how T-cell receptors are able to seek out and bind to rare foreign peptides among many irrelevant interactions, all with low apparent binding affinity. The research sheds light on how T cells recognize their targets and on strategies for immunotherapies.

This research was supported by the National Institutes of Health (grants AI100643, AI037581, GM004746).

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