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KIR2DS1-mediated activation overrides NKG2A-mediated inhibition in HLA-C C2-negative individuals.
Int Immunol 2008; 20(4):555-63II

Abstract

NK cell cytotoxicity is controlled through a balance of both activating and inhibitory signals. The HLA specificity of alloreactive NK cells has been previously shown to be controlled by inhibitory killer immunoglobulin-like receptors (KIRs). Alloreactive NK cells lyse targets that lack the HLA ligand for their inhibitory KIR. We have characterized in detail an alloreactive NK clone in which the specificity is controlled by an activating receptor, KIR2DS1. Only target cells expressing the HLA-C group 2 (C2) epitope were lysed by this clone and homozygous C2 targets were lysed more strongly than heterozygous C1/C2 targets. Anti-CD158a (KIR2DS1) blocked lysis of targets confirming KIR2DS1 was responsible. Although this NK clone expressed NKG2A, an inhibitory receptor whose ligand is HLA-E, targets with ligands for both KIR2DS1 and NKG2A were lysed by this clone indicating that the KIR2DS1-mediated activation signal overrides the NKG2A-mediated inhibitory signal. KIR2DS1 activated NK clones in polyclonally expanded NK cultures from a donor that lacked the C2 epitope accounted for approximately 1% of all NK cells. This study highlights a potential role for NK cells controlled by activating KIR in mediating NK alloreactivity.

Authors+Show Affiliations

Department of Clinical Immunology and Immunogenetics, PathWest Laboratory Medicine, Royal Perth Hospital, Perth, Western Australia, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18308713

Citation

Foley, Bree, et al. "KIR2DS1-mediated Activation Overrides NKG2A-mediated Inhibition in HLA-C C2-negative Individuals." International Immunology, vol. 20, no. 4, 2008, pp. 555-63.
Foley B, De Santis D, Lathbury L, et al. KIR2DS1-mediated activation overrides NKG2A-mediated inhibition in HLA-C C2-negative individuals. Int Immunol. 2008;20(4):555-63.
Foley, B., De Santis, D., Lathbury, L., Christiansen, F., & Witt, C. (2008). KIR2DS1-mediated activation overrides NKG2A-mediated inhibition in HLA-C C2-negative individuals. International Immunology, 20(4), pp. 555-63. doi:10.1093/intimm/dxn013.
Foley B, et al. KIR2DS1-mediated Activation Overrides NKG2A-mediated Inhibition in HLA-C C2-negative Individuals. Int Immunol. 2008;20(4):555-63. PubMed PMID: 18308713.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - KIR2DS1-mediated activation overrides NKG2A-mediated inhibition in HLA-C C2-negative individuals. AU - Foley,Bree, AU - De Santis,Dianne, AU - Lathbury,Louise, AU - Christiansen,Frank, AU - Witt,Campbell, Y1 - 2008/02/27/ PY - 2008/3/1/pubmed PY - 2008/9/9/medline PY - 2008/3/1/entrez SP - 555 EP - 63 JF - International immunology JO - Int. Immunol. VL - 20 IS - 4 N2 - NK cell cytotoxicity is controlled through a balance of both activating and inhibitory signals. The HLA specificity of alloreactive NK cells has been previously shown to be controlled by inhibitory killer immunoglobulin-like receptors (KIRs). Alloreactive NK cells lyse targets that lack the HLA ligand for their inhibitory KIR. We have characterized in detail an alloreactive NK clone in which the specificity is controlled by an activating receptor, KIR2DS1. Only target cells expressing the HLA-C group 2 (C2) epitope were lysed by this clone and homozygous C2 targets were lysed more strongly than heterozygous C1/C2 targets. Anti-CD158a (KIR2DS1) blocked lysis of targets confirming KIR2DS1 was responsible. Although this NK clone expressed NKG2A, an inhibitory receptor whose ligand is HLA-E, targets with ligands for both KIR2DS1 and NKG2A were lysed by this clone indicating that the KIR2DS1-mediated activation signal overrides the NKG2A-mediated inhibitory signal. KIR2DS1 activated NK clones in polyclonally expanded NK cultures from a donor that lacked the C2 epitope accounted for approximately 1% of all NK cells. This study highlights a potential role for NK cells controlled by activating KIR in mediating NK alloreactivity. SN - 1460-2377 UR - https://www.unboundmedicine.com/medline/citation/18308713/KIR2DS1_mediated_activation_overrides_NKG2A_mediated_inhibition_in_HLA_C_C2_negative_individuals_ L2 - https://academic.oup.com/intimm/article-lookup/doi/10.1093/intimm/dxn013 DB - PRIME DP - Unbound Medicine ER -