Antigens are a critical part of how the immune system works; they are present on many types of cells, and can be made of proteins, lipids, sugars, and other substances. Antigens are presented to immune cells, and recognized through binding; they can link up with receptors on T cells or antibodies. They are how the immune system identifies foreign invaders or dangerous substances that have to be eliminated from the body. Scientists have now learned more about how T cells identify antigens that are lipids, changing long-held assumptions about the process. The findings have been reported in Nature Communications.
Molecules known as CD1s present lipids to T cells. It’s been assumed that antigens sit upright when they are displayed to T cells, in an end-to-end orientation that was thought to be a universal interaction between antigens and immune cells.
But this study used advanced imaging tools to show that one type of CD1 known as CD1c is able to present lipids in a variety of ways. There does not seem to be a single presentation method for antigens. Instead, the immune system is able to monitor various displays, and CD1c is able to present lipids in a sideways position.
"Much of immunology has been built around the idea that immune recognition follows one fixed arrangement," said co-senior study author Dr. Adam Shahine, a NHMRC research fellow at Monash University. "This work shows that the immune system is more flexible than we assumed, and that there are additional ways immune cells can see what's around them."
CD1c can be effectively checked with this orientation, and is able to manipulate larger molecules by moving one portion sideways, while T cells are still able to recognize it. This method can also work with different lipids.
"Using data collected at the ANSTO Australian Synchrotron, we found that CD1c can hold multiple lipids in place at the same time, in unique configurations, but can position them in a manner that still allows immune cells to engage," explained first study author Dr. Thinh-Phat Cao, also of Monash University. "That flexibility helps explain how the immune system can deal with such a wide variety of lipid molecules, shaping immune responses in unexpected ways."
Additional work showed that CD1c is able to bind to many types of lipids, and it may use various orientations for displaying different kinds of lipids.
"This discovery opens new avenues to better understand how diseases where lipids play a role," added Shahine. "This could aid in the design of treatments that are better matched to how the body responds to disease."
Sources: Monash University, Nature Communications
