A new ‘clutch’ to engage the immune cell ‘gear’

Two adaptor proteins act like a clutch, help protein condensates get into the correct slot

Microscopic mystery: If the clutch is not active in the immune cells, they are unable to respond to the information from the outside, says Satyajit Mayor (right).

A unique summer institute held at the Woods Hole Marine Biological Laboratory in the U.S. (during 2013-2018) helped unlock a few mysteries of the immune system. A team of leading biologists and biochemists identified a molecular ‘clutch’ which helps move clusters of proteins inside the immune cells.

Signalling machinery

The main aim of the study was to understand how the T-cell receptors, which play a main role in our immunity, form a signalling complex and how they build a signalling machinery that picks up information from the outside and use it to activate the immune mechanism.

The team identified two adaptor proteins which act as clutch and help protein condensates get into the correct slot.

Protein condensates are a form of a macromolecular assembly formed by multivalent proteins coming together to create a region that is highly concentrated. It is in the form of a phase separated patch, like oil droplets that form a distinct patch on water.

The recruitment of these adaptor proteins to the condensates was found to be influenced by where the T-cell receptor clusters are located.

“When a T-cell receptor binds to an antigen, the T-cell undergoes a global reorganisation forming a signalling centre at the site of the antigen-bound receptor. The continuous transport of the studied protein condensates towards this signalling centre is important for maintaining the signalling output which is part of the immune response,” adds Prof. Darius Vasco Köster from the Marine Biological Laboratory at Woods Hole, U.S. in an email to The Hindu . He is one of the authors of the work published in the journal eLife.

The adaptor proteins also promoted association of the protein condensates with actin present inside the cell.

Crucial role

Actin plays a crucial role in cellular processes required for normal immune function. “We fully don’t know the implications of the function of these proteins, but we know that if the clutch is not active in the immune cells, they are unable to respond to the information from the outside. These adaptors are also quite general, they go and adapt to other processes as well,” says Prof. Satyajit Mayor, from the National Centre for Biological Sciences, Bengaluru, and one of the authors.

Understanding the cascade of events that take place in the immune cells can help develop new vaccines and treatment regimens.