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Diverse human NK cell repertoires of polymorphic MHC‐specific inhibitory receptor expression are structured by strength of receptor‐ligand interactions towards equilibrium of missing‐self response
Author(s) -
Yawata Makoto,
Yawata Nobuyo,
Draghi Monia,
Partheniou Fotini,
Little AnnMargaret,
Parham Peter
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.550
Subject(s) - receptor , human leukocyte antigen , biology , major histocompatibility complex , flow cytometry , immunology , microbiology and biotechnology , inhibitory postsynaptic potential , immune system , genetics , antigen , neuroscience
The structure and function of diverse human NK cell repertoires were studied by investigating the variegated expression of six inhibitory HLA‐specific receptors (NKG2A, KIR2DL1, 2DL3, 3DL1, 3DL2 and LILRB1) using 13‐parameter flow cytometry in a panel of 58 donors. Response of NK subsets against HLA class I deficient 721.221 cells were evaluated using intracellular staining for gamma IFN and CD107 mobilization. In all donors, all 64 subsets of NK cells defined by the possible combinations of these receptors were detected, demonstrating that there is no wholesale deletion of any subset. Of note, 2–15% of NK cells lacked all six receptors. Repertoire structures were unique to each individual and NK subsets differed in their enhancement of missing‐self. Enhancement by KIR varied substantially according to KIR and HLA allotype combinations, reflecting the differences in interaction between inhibitory receptors and ligands. This contrasted to the enhancement conferred by NKG2A which was constant and of intermediate strength. Through this complementary action of conserved NKG2A and variable KIR, a diversity of human NK cell repertoires is formed. The analyses present a new perspective on the diverse character of human NK repertoires which impact the NK cell response against infection, malignancy, in reproduction and in allogeneic transplantation.