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

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 IFN 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 IFN 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.

HLA-DR Expression in Natural Killer Cells Marks Distinct Functional States, Depending on Cell Differentiation Stage

“…It has been demonstrated that TIM-3 substantially decreases after NK cell activation [40], followed by reduced cytotoxicity and IFNγ production [40]. KLRB1 (CD161), another inhibitory NK cell receptor, characterizes less differentiated NK cells [41]; thus, its downregulation should be associated with a more mature state, as shown for hCMV-associated adaptive NK cells [42]. TMIGD2-an activating NK cell and T cell receptor interacting with HHLA2 [43]-is mostly expressed on naive T cells, while memory cells lose their expression [44]; therefore, their downregulation may be associated with the memory NK cell phenotype.…”