# Adaptive NKG2C+ NK cells in cytomegalovirus seropositive individuals predominantly lack NKR‐P1A receptor expression

## TL;DR

CMV infection leads to the expansion of a specific type of NK cell that lacks the NKR-P1A receptor, highlighting how CMV shapes the immune system.

## Contribution

The study reveals that NKR-P1A-negative NK cells expand during CMV infection due to increased activation and proliferation.

## Key findings

- Adaptive NKG2C+ NK cells lacking NKR-P1A show increased activation and proliferation in CMV-infected individuals.
- NKR-P1A-negative NK cells exhibit transcriptome signatures of adaptive NK cells during CMV infection.
- CMV infection induces distinct gene expression profiles in NKR-P1A+ and NKR-P1A- NK cells.

## Abstract

The impact of cytomegalovirus (CMV) infection in shaping natural killer (NK) cell receptor (NKR) repertoire highlights the importance of NKRs in immunity against CMV. NKR‐P1A (CD161) is an inhibitory NKR, whose expression is lost during CMV infection, but its role in NK cell responses during CMV infection is not known. Here, we show selective expansion of adaptive NKG2C+ NK cells lacking NKR‐P1A receptor (NKR‐P1A‒) due to their increased activation and proliferation compared with NKR‐P1A+ NK cells in CMV‐infected individuals. In vitro stimulation of PBMCs showed similar inherent proliferative capacity in both NKR‐P1A+ versus NKR‐P1A‒ NK cells in steady state and upregulation, but not loss of NKR‐P1A receptor expression, in sorted NK cells. Furthermore, CMV infection induced differential gene expression profiles in NKR‐P1A+ versus NKR‐P1A‒ NK cells, and only NKR‐P1A‒ NK cells exhibited transcriptome signatures associated with adaptive NK cells in CMV‐infected individuals. This study further highlights the impact of CMV infection in shaping NK cell receptor repertoire and exclusion of NK cells that express the NKR‐P1A receptor from the adaptive NKG2C+ NK cell population that expands during CMV infection.

Expansion of the adaptive NKG2C+ NK cells during cytomegalovirus (CMV) infection is restricted to the subset lacking NKR‐P1A receptor. This is associated with increased proliferation of NKR‐P1A‒, but not NKR‐P1A+, NK cells in CMV‐infected individuals.