Researchers discover possible origins of "old" immunological memory

Natural killer cells are part of the innate immune system. Their role is to detect the cells infected by the virus and destroy them. When an infection is detected, a small subset of the most effective killer cells is selectively identified and expanded – as currently shown by a team from the Technical University of Munich (TUM). This could represent a simple and evolutionary old form of immunological memory.

More than half of the world's population is infected with cytomegalovirus (CMV), which remains in the body for life. Normally, these infections produce no symptoms. With T cells, natural killer cells (NK) effectively control the virus, although it can cause serious illness in people with weakened immune systems. NKs have surface molecules that identify CMV-infected cells, such as the Ly49H receptor in mice. NKs with this receptor (Ly49H-NKs) are known to be particularly effective at destroying CMV-infected cells.

The amount of receptors determines the efficiency

Dr. Veit Buchholz, head of research group at the Institute of Medical Microbiology, Immunology and Hygiene at TUM, and his colleague Dr. Simon Grbadmann, have undertaken to determine what 39 It happens to these Ly49H-NK during a CMV infection. To do this, they monitored the individual Ly49H-NK-derived immune responses in CMV-infected mice.

They found that Ly49H N49 replication was extremely varied. This variation correlated with the distinct surface expression levels of Ly49H itself. Cells with higher expression of Ly49H developed further and were thus able to more effectively control CMV. This trait appeared to be inherited, with the descendants of an NK resembling their "mother" cell in terms of Ly49H receptor levels. The inheritance of such quantitative traits has never been observed before in NK.

"Old" immunological memory index

The really interesting aspect was that even after the peak of the immune response, killer cells expressing large amounts of Ly49H remained detectable at high numbers. "

Dr. Simon Grbadmann

He goes on to explain that this is an important indication of the existence of a simple immunological memory based on basic knowledge.

Immunological memory can only work if there is an available selection mechanism that multiplies and then preserves the most effective cells to fight an infection. "We show that in NKs – which are part of the old and evolving innate immune system – the amount of receptor alone is a sufficient criterion to drive selection to a simple level," Buchholz emphasizes. This discovery could also be significant for humans because human NKs possess an equivalent receptor, which plays an important role during CMV infection.

Fluorescent Protein Bar Code

Grbadmann, in collaboration with medical student Ludwig Pachmayr, has developed the appropriate tool for tracking NK in living organisms as part of TUM's "Translational Medicine" doctoral program: up to 30 NK individuals and their descendants. The researchers then want to know how the NKs transmit information on the amount of receptors to their descendants. NKs are considered a possible alternative to T cells for immunotherapy of infections and tumor diseases.

Source:

http://www.tum.de/nc/en/about-tum/news/press-releases/details/article/35474/

Journal reference:

Grbadmann, S. et al. (2019) Separate Surface Expression of the Activating Receptor Ly49H Causes Differential Expansion of NK Cell Clones on Murine Cytomegalovirus Infection. Immunity. doi.org/10.1016/j.immuni.2019.04.015.