Peptide-specific engagement of the activating NK cell receptor KIR2DS1
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Peptide-specific engagement of the activating NK cell receptor KIR2DS1. / Chapel, Anaïs; Garcia-Beltran, Wilfredo F; Hölzemer, Angelique; Ziegler, Maja; Lunemann, Sebastian; Martrus, Gloria; Altfeld, Marcus.
In: SCI REP-UK, Vol. 7, No. 1, 25.05.2017, p. 2414.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Peptide-specific engagement of the activating NK cell receptor KIR2DS1
AU - Chapel, Anaïs
AU - Garcia-Beltran, Wilfredo F
AU - Hölzemer, Angelique
AU - Ziegler, Maja
AU - Lunemann, Sebastian
AU - Martrus, Gloria
AU - Altfeld, Marcus
PY - 2017/5/25
Y1 - 2017/5/25
N2 - The activating NK cell receptor KIR2DS1 has been shown to be involved in many disorders including autoimmune diseases, malignancies and pregnancy outcomes. However, the precise ligands and functions of this receptor remain unclear. We aimed to gain a better understanding of the factors involved in the binding of KIR2DS1 and its inhibitory counterpart KIR2DL1 to HLA class I molecules, and the consequences for KIR2DS1+ NK-cell function. A systematic screen that assessed binding to 97 HLA-I proteins confirmed that KIR2DS1-binding was narrowly restricted to HLA-C group 2 complexes, while KIR2DL1 showed a broader binding specificity. Using KIR2DS1ζ+Jurkat reporter-cells and peptide-pulsed 721.221.TAP1KO-HLA-C*06:02 cells, we identified the synthetic peptide SRGPVHHLL presented by HLA-C*06:02 that strongly engaged KIR2DS1- and KIR2DL1-binding. Functional analysis showed that this HLA-C*06:02-presented peptide can furthermore activate primary KIR2DS1(+) NK cell clones. Thus, we demonstrated peptide-dependent binding of the activating NK cell receptor KIR2DS1, providing new insights into the underlying mechanisms involved in KIR2DS1-related disorders.
AB - The activating NK cell receptor KIR2DS1 has been shown to be involved in many disorders including autoimmune diseases, malignancies and pregnancy outcomes. However, the precise ligands and functions of this receptor remain unclear. We aimed to gain a better understanding of the factors involved in the binding of KIR2DS1 and its inhibitory counterpart KIR2DL1 to HLA class I molecules, and the consequences for KIR2DS1+ NK-cell function. A systematic screen that assessed binding to 97 HLA-I proteins confirmed that KIR2DS1-binding was narrowly restricted to HLA-C group 2 complexes, while KIR2DL1 showed a broader binding specificity. Using KIR2DS1ζ+Jurkat reporter-cells and peptide-pulsed 721.221.TAP1KO-HLA-C*06:02 cells, we identified the synthetic peptide SRGPVHHLL presented by HLA-C*06:02 that strongly engaged KIR2DS1- and KIR2DL1-binding. Functional analysis showed that this HLA-C*06:02-presented peptide can furthermore activate primary KIR2DS1(+) NK cell clones. Thus, we demonstrated peptide-dependent binding of the activating NK cell receptor KIR2DS1, providing new insights into the underlying mechanisms involved in KIR2DS1-related disorders.
KW - Journal Article
U2 - 10.1038/s41598-017-02449-x
DO - 10.1038/s41598-017-02449-x
M3 - SCORING: Journal article
C2 - 28546555
VL - 7
SP - 2414
JO - SCI REP-UK
JF - SCI REP-UK
SN - 2045-2322
IS - 1
ER -