T-cells seem to follow maths
New research suggests our T-cell immune response depends on specific mathematics.
An international research team has found that the way immune cells pick friends from foes can be described by a classic maths puzzle known as the “narrow escape problem”.
The narrow escape problem is a framework often applied in cellular biology. It posits randomly moving particles trapped in a space with only a tiny exit, and calculates the average time required for each one to escape.
A collaborative study between biologists, immunologists and mathematicians has analysed how potential pathogens are probed by T-cells, which identify and attack invaders.
The researchers discovered that the equations used in the narrow escape problem play a key role in determining whether an immune response is triggered.
“The narrow escape problem turns out to be a close cousin of the situation with T cell receptors,” says co-author Justin Tzou from Macquarie University.
“It is about determining how long a diffusing particle remains in a certain region before escaping.”
The unique shape of T-cells creates what has been termed a “close-contact zone” for triggering molecules called T-cell receptors. Unlike most cells, which have relatively smooth surfaces, T-cells are covered in ruffles, bumps and other protrusions.
T-cell receptor molecules sit on the surface of the cells to recognise enemies and trigger a hostile response.
The receptors contain molecular patterns that mirror those found on the surfaces of bacteria, tumours, and other dangerous interlopers. But exactly how the process of recognition and triggering works – and particularly how it works so quickly and accurately – has been a mystery.
The researchers believe the unusually lumpy shape of the T-cell plays a vital role.
The protrusions on the surface mean that its area of contact with a potential enemy cell is very small – only a couple of hundred nanometres across.
And according to the new theory, T-cell receptors follow a two-second rule: if they spend more than two seconds in the small contact zone, a chemical process begins to sound the alarm and trigger an attack.
The size of the contact zone depends on the size of the bumps on the surface of the T-cell.
“The smaller the zone, the less likely the T-cell receptor is able to stay in that zone by chance, triggering an attack,” Dr Tzou says.
“It looks like the size of these protrusions keeps the process sensitive to the presence of the invader.”