EBV Infection Alters NK Cell Phenotype Distinctly From hCMV

Area of Science:

• Immunology
• Virology
• Cellular Biology

Background:

• Natural killer (NK) cells are crucial for antiviral immunity, utilizing receptors like NKG2 and KIR to interact with HLA-I molecules.
• While NK cell adaptation to human cytomegalovirus (hCMV) is known, their response to Epstein-Barr virus (EBV) and the role of KIR-HLA combinations in healthy carriers are less understood.

Purpose of the Study:

• To investigate the differential impact of hCMV and EBV infections on NK cell subsets and their receptor expression in healthy adults.
• To explore the association between specific KIR-HLA combinations and NK cell responses to hCMV and EBV.

Main Methods:

• High-resolution HLA genotyping was performed on 85 healthy adult donors.
• Phenotypic profiling of NK cell subsets and serological testing for hCMV and EBV-specific IgG were conducted.
• Statistical analyses were used to correlate NK cell subset frequencies and receptor expression with viral IgG titers and HLA-KIR genotypes.

Main Results:

• hCMV-seropositive individuals showed expansions of NKG2C+ and HLA-DR+ NK cells, correlating with hCMV-IgG titers.
• EBV infection was linked to increased frequencies of terminally differentiated CD56dim, NKG2A-, CD57+ NK cells and elevated inhibitory KIR expression.
• EBV-IgG titers correlated with CD57 and KIR2DS4 levels, and carriage of HLA-C2 alleles in KIR2DS4+ donors was associated with higher EBV-IgGs.

Conclusions:

• hCMV and EBV infections induce distinct NK cell adaptive responses.
• The interplay between HLA class I and KIR molecules significantly shapes NK cell immunity against EBV in healthy individuals.