The impact of SARS-CoV-2 peptides on activation of NK cells

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

BACKGROUND: NK cells, alone with T lymphocytes, have a high antiviral activity. Exploring the contribution of NK cells in fighting SARS-CoV-2 infection may promote the development of appropriate treatments for COVID-19. Previously, NK cell response was considered nonspecific, provided by a combination of signals from activating and inhibitory receptors. Currently, the existence of certain subpopulations of antigen-specific, or adaptive, NK cells has been shown.

AIM: To evaluate the functional response of NK cells induced by SARS-CoV-2 peptides.

MATERIALS AND METHODS: The functional response of NK cells to SARS-CoV-2 peptides was determined by their degranulation (surface CD107a expression) and IFNγ production levels, and by the activation degree (HLA-DR expression level). Volunteers who recovered from COVID-19 participated in the study, and immune cells from a healthy volunteer without SARS-CoV-2-specific antibodies were used as controls.

RESULTS: NK cells from individuals who had recovered from COVID-19, in contrast to a donor who had not been infected, showed a higher level of IFNγ production in response to SARS-CoV-2 peptides, compared with control samples. The level of degranulation of NK cells from donors previously infected with SARS-CoV-2 was higher than in the corresponding control. The proportion of activated NK cells obtained from recovered donors was also higher in samples stimulated with SARS-CoV-2 peptides.

CONCLUSIONS: We have demonstrated the activation of NK cells obtained from people who had previously recovered from COVID-19 in response to SARS-CoV-2 peptide antigens in cultures of peripheral mononuclear cells in vitro. This study reveals the possibility for further investigation of antigen-specific NK cells in COVID-19 disease. The use of such cells could help develop treatments for SARS-CoV-2 infection.

Full Text

Restricted Access

About the authors

Maria O. Ustiuzhanina

Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; Skolkovo Institute of Science and Technology

Author for correspondence.
Email: mashaust1397@gmail.com
ORCID iD: 0000-0003-3378-6508

Postgraduate Student, Center of Life Science; Engineer

Russian Federation, Moscow; Moscow

Olga V. Britanova

Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: olbritan@gmail.com
ORCID iD: 0000-0002-6295-1392

Cand. Sci. (Biol.), Senior Research Associate

Russian Federation, Moscow

Elena I. Kovalenko

Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: lenkovalen@mail.ru
ORCID iD: 0000-0001-8119-8247
SPIN-code: 2359-7599
Scopus Author ID: 7102778244
ResearcherId: S-2086-2016

Cand. Sci. (Biol.), Senior Research Associate

Russian Federation, Moscow

References

  1. Sivori S, Vacca P, Del Zotto G, et al. Human NK cells: surface receptors, inhibitory checkpoints, and translational applications. Cell Mol Immunol. 2019;16(5):430–441. doi: 10.1038/s41423-019-0206-4
  2. Paust S, von Andrian UH. Natural killer cell memory. Nat Immunol. 2011;12(6):500–508. doi: 10.1038/ni.2032
  3. Gumá M, Budt M, Sáez A, et al. Expansion of CD94/NKG2C+ NK cells in response to human cytomegalovirus-infected fibroblasts. Blood. 2006;107(9):3624–3631. doi: 10.1182/BLOOD-2005-09-3682
  4. Hammer Q, Rückert T, Borst EM, et al. Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells article. Nat Immunol. 2018;19:453–463. doi: 10.1038/S41590-018-0082-6
  5. Kovalenko EI, Streltsova MA, Kanevskiy LM, et al. Identification of human memory-like NK cells. Curr Protoc Cytom. 2017;79:9.50.1–9.50.11. doi: 10.1002/CPCY.13
  6. Wijaya RS, Read SA, Truong NR, et al. HBV vaccination and HBV infection induces HBV-specific natural killer cell memory. Gut. 2021;70(2):357–369. doi: 10.1136/GUTJNL-2019-319252
  7. Maucourant C, Filipovic I, Ponzetta A, et al. Natural killer cell immunotypes related to COVID-19 disease severity. Sci Immunol. 2020;5(50):eabd6832. doi: 10.1126/SCIIMMUNOL.ABD6832

Supplementary files

Supplementary Files
Action
1. JATS XML
2. Fig. 1. Investigation of IFNγ production in response to stimulation with SARS-CoV-2 peptides. IFNγ production in the presence or absence of IL-2 stimulation by: а — NK cells, representative cytometric data of one donor who recovered from COVID-19 is presented; b — NK cells obtained from donors who recovered from COVID-19, gates were used to isolate CD56+CD3– cells; c — T-cells obtained from donors who recovered from COVID-19; gates were used to isolate CD3+ cells; d — subpopulations of NK cells; representative cytometric data of one donor who recovered from COVID-19 are presented; e — NK cells obtained from one donor, measured twice, 6 and 18 months after SARS-CoV-2 infection; f — NK cells, shows the cytometric data of one donor who was not infected with SARS-CoV-2. * p < 0.05

Download (509KB)
3. Fig. 2. Degranulation and activation of NK cells: a — level of CD107a on the surface of NK cells, representative cytometric data from one donor who recovered from COVID-19; b — CD107a level on the surface of NK cells obtained from donors who recovered from COVID-19 using gates, CD56+CD3– cells were isolated, green square symbols highlight the data of one donor; c — the level of HLA-DR expression on the surface of NK cells obtained from donors who recovered from COVID-19; d — using gates CD56+CD3– cells were isolated; the level of CD107a on the surface of NK cells, one donor, measured twice, 6 and 18 months after SARS-CoV-2 infection; e — representative cytometric data of comparison of the level of CD107a on the surface of CD56+CD3– with live CD56+CD3–SYTOX– cells; f — CD107a expression level on the surface of NK cells, cytometric data of a SARS-CoV-2 seronegative donor are presented. * p < 0.05; ** p < 0.0005

Download (563KB)

Copyright (c) 2022 Eco-Vector



СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 74760 от 29.12.2018 г.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies