Why natural killer cells react to COVID-19

Date:
February 22, 2022
Source:
Karolinska Institutet
Summary:
Little has been known to date about how the immune system's
natural killer (NK) cells detect which cells have been infected
with SARS-CoV-2.

Scientists now show that NK cells respond to a certain peptide on
the surface of infected cells. The study is an important piece of
the puzzle in our understanding of how the immune system reacts
to COVID-19.



FULL STORY ========================================================================== Little has been known to date about how the immune system's natural killer
(NK) cells detect which cells have been infected with SARS-CoV-2. An international team of scientists led by researchers from Karolinska
Institutet in Sweden now shows that NK cells respond to a certain peptide
on the surface of infected cells. The study, which is published in Cell Reports, is an important piece of the puzzle in our understanding of
how the immune system reacts to COVID-19.


==========================================================================
NK cells are white blood cells that are part of the innate immune system.

Unlike cells in the adaptive immune defence, they are able to recognise
and kill cancer cells and virus-infected cells immediately without having encountered them before. This ability is controlled by a balance between
the NK cells' activating and inhibiting receptors, which can react to
different molecules on the surface of other cells.

The virus is revealed by a peptide A new study shows why certain NK cells
are activated when encountering a cell infected with SARS-CoV-2. The
infected cells contain a peptide from the virus that triggers a reaction
in NK cells that carry a particular receptor, NKG2A, able to detect
the peptide.

"Our study shows that SARS-CoV-2 contains a peptide that is displayed
by molecules on the cell surface," says Quirin Hammer, researcher at
the Center for Infectious Medicine (CIM), Karolinska Institutet. "The activation of NK cells is a complex reaction, and here the peptide blocks
the inhibition of the NK cells, which allows them to be activated. This
new knowledge is an important piece of the puzzle in our understanding of
how our immune system reacts in the presence of this viral infection."
The study was a major collaboration between Karolinska Institutet,
Karolinska University Hospital and research laboratories and universities
in Italy, Germany, Norway and the USA. The first phase was to test their hypothesis using computer simulations that were then confirmed in the laboratory. The decisive phase was the infection of human lung cells
with SARS-CoV-2 in a controlled environment, whereupon the researchers
could show that NK cells with the receptor in question are activated to
a greater degree than the NK cells without it.

Monitoring new virus variants "These findings are important to
our understanding of how immune cells recognise cells infected with SARS-CoV-2," says Dr Hammer. "This may become significant when monitoring
new virus variants with the aim to determine how well the immune system responds to them." The study is now being followed up with the help of
a biobank at Karolinska University Hospital and Karolinska Institutet containing blood samples from over 300 people treated for COVID-19 during
the first wave of the pandemic.

"We'll be examining if the composition of NK cells a person has
contributes to how severe their symptoms are when infected with
SARS-CoV-2," he continues.

The study was financed by the EU, Deutsche Forschungsgemeinschaft (DFG),
the Karolinska Institutet Foundation for Virus Research, the Petrus and
Augusta Hedlund Foundation, the Clas Groschinsky Memorial Foundation, the
Lars Hierta Memorial Foundation, the Tornspiran Foundation, the Swedish
Cancer Society, the Norwegian Research Council, the Swedish Research
Council, the Knut and Alice Wallenberg Foundation and Nordstjernan
AB. Co-author Hans-Gustaf Ljunggren is a member of the board of XNK Therapeutics AB and Vycellix Inc. Karl-Johan Malmberg is scientific
advisor for and has a research grant from Fate Therapeutics, and is a
member of Vycellix Inc's scientific advisory board.

========================================================================== Story Source: Materials provided by Karolinska_Institutet. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Quirin Hammer, Josefine Dunst, Wanda Christ, Francesca Picarazzi,
Mareike
Wendorff, Pouria Momayyezi, Oisi'n Huhn, Herman K. Netskar, Kimia T.

Maleki, Marina Garci'a, Takuya Sekine, Ebba Sohlberg, Valerio
Azzimato, Myriam Aouadi, Frauke Degenhardt, Andre Franke, Francesco
Spallotta, Mattia Mori, Jakob Michae"lsson, Niklas K. Bjo"rkstro"m,
Timo Ru"ckert, Chiara Romagnani, Amir Horowitz, Jonas Klingstro"m,
Hans-Gustaf Ljunggren, Karl-Johan Malmberg. SARS-CoV-2 Nsp13
encodes for an HLA-E- stabilizing peptide that abrogates inhibition
of NKG2A-expressing NK cells. Cell Reports, 2022; 110503 DOI:
10.1016/j.celrep.2022.110503 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220222135226.htm

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