Biochemical controls: how MAIT T cells work (Introduction)

by David Turell , Saturday, November 11, 2023, 17:48 (376 days ago) @ David Turell

Extremely specialized:

https://medicalxpress.com/news/2023-11-closer-rebel-cells-mait.html

"Most T cells only work in the person who made them. Your T cells fight threats by responding to molecular fragments that belong to a pathogen—but only when these molecules are bound with markers that come from your own tissues. Your influenza-fighting T cells can't help your neighbor, and vice versa.

"'However, we all have T cells that do not obey these rules," says LJI Professor and President Emeritus Mitchell Kronenberg, Ph.D. "One of these cell types is mucosal-associated invariant T.

"Now Kronenberg and his LJI colleagues have uncovered another MAIT cell superpower: MAIT cells can recognize the same markers whether they come from humans or mice. Kronenberg calls this finding "astounding." "Humans diverged from mice in evolution 60 million years ago," he says.

***

"Kronenberg was initially interested in MAIT cells because of their unexpected response speed. Typical T cells need a few days to develop in the thymus and only adapt to fighting new threats after leaving the thymus—and after several days of stimulation from a pathogen. MAIT cells are much faster because they can respond to more generic markers of infection, rather than hunting for very specific tissue-type markers. For MAIT cells, a red flag is a red flag, no matter who is waving it.

"This broad specificity makes MAIT cells similar to the immune system's first-responder cells, such as macrophages and neutrophils, which make up the "innate" immune system. "MAIT cells have this 'innate-like' characteristic," says Ascui. "They're like your first line of defense." In fact, MAIT cells tend to gather in tissues like the lungs and intestines, where the body is under constant threat from airborne and foodborne pathogens.

"The new study shows that MAIT cells don't just recognize a range of markers within one person. Instead, these odd T cells can "see" markers shared between humans—and even between species. Scientists call these kinds of shared markers "conserved." There has been no reason for the markers to change over the eons, so they remain the same across related species. (my bold)

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"...after a bacterial infection, MAIT1 and MAIT17 cells persist but become super-charged, or capable of having greater protective function for months. These cytokines help the MAIT cells take aim at different threats. MAIT1 cells target viruses such as influenza, while MAIT17 cells are better at targeting bacteria.

"In the new study, the team found that MAIT cells from both species are more capable of taking up and storing fat, compared with typical T cells. This finding suggests MAIT cells are more dependent on this nutrient for energy. This discovery is also in line with previous work in the Kronenberg Lab showing that some MAIT cells depend on fat to fight pathogens. The key difference between the species was that human MAIT cells can produce interferon-gamma and IL-17, but not evidently by separate cell populations.

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"The team also compared MAIT cells found in different parts of the body, such as the blood, thymus (where T cells, including MAIT cells, develop), and the lung and spleen (where MAIT cells camp out). They discovered that MAIT cells still in the thymus look very similar between humans and mice ("dirty" or not); however, MAIT cells from the lungs and blood are more different between humans and lab mice.

"MAIT cells from the "dirty" mice fell between the two groups, adding to the evidence that more natural-like environments change how MAIT cells develop and learn to target disease.

'"Environmental, as well as genetic differences, shape the species differences in these cells," says Kronenberg."

Comment: note my bold. These cells appeared early in evolution, again showing purposeful design in an invaluable immune system.