Polygenic polymorphisms cooperate to drive expansion of HCMV adaptive NK cell and NK-like T cell populations

In 200 healthy donors with HCMV infection, cumulative NKG2C copy number with CD16a and HLA-E alleles shapes NKG2C+ adaptive NK and NK-like T cell repertoires.

• Why it matters: HCMV expands adaptive innate-like lymphocytes in only 30–40% of infected people, and the immunogenetic rules governing this selective expansion and function are unclear.
• What they did: The study genotyped immunogenetic loci across three NKG2C-high lymphocyte populations and linked NKG2C (KLRC2) copy number and allelic variants, plus CD16a and HLA-E polymorphisms, to NKG2C expression and ADCC-related responses.
• The result: NKG2C copy number associated with NKG2C+ NK frequency and density in HCMV- but not HCMV+ individuals, while among HCMV+ donors CD16a and HLA-E acted cumulatively; HLA-E*01:03 reduced NKG2C-linked NK responsiveness and CD16a polymorphism altered ADCC strength in NKG2C+ TCRβ+CD8+ T cells.

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