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Structure of the human activating natural cytotoxicity receptor NKp30 bound to its tumor cell ligand B7-H6

Natural killer (NK) cells are lymphocytes of the innate immune system that participate in the elimination of tumor cells. In humans, the activating natural cytotoxicity receptors (NCRs) NKp30, NKp44, and NKp46 play a major role in NK cell–mediated tumor cell lysis. NKp30 recognizes B7-H6, a member o...

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Autores principales: Li, Yili, Wang, Qian, Mariuzza, Roy A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135353/
https://www.ncbi.nlm.nih.gov/pubmed/21422170
http://dx.doi.org/10.1084/jem.20102548
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author Li, Yili
Wang, Qian
Mariuzza, Roy A.
author_facet Li, Yili
Wang, Qian
Mariuzza, Roy A.
author_sort Li, Yili
collection PubMed
description Natural killer (NK) cells are lymphocytes of the innate immune system that participate in the elimination of tumor cells. In humans, the activating natural cytotoxicity receptors (NCRs) NKp30, NKp44, and NKp46 play a major role in NK cell–mediated tumor cell lysis. NKp30 recognizes B7-H6, a member of the B7 family which is expressed on tumor, but not healthy, cells. To understand the basis for tumor surveillance by NCRs, we determined the structure of NKp30, a member of the CD28 family which includes CTLA-4 and PD-1, in complex with B7-H6. The overall organization of the NKp30–B7-H6–activating complex differs considerably from those of the CTLA-4–B7 and PD-1–PD-L T cell inhibitory complexes. Whereas CTLA-4 and PD-1 use only the front β-sheet of their Ig-like domain to bind ligands, NKp30 uses both front and back β-sheets, resulting in engagement of B7-H6 via the side, as well as face, of the β-sandwich. Moreover, B7-H6 contacts NKp30 through the complementarity-determining region (CDR)–like loops of its V-like domain in an antibody-like interaction that is not observed for B7 or PD-L. This first structure of an NCR bound to ligand provides a template for designing molecules to stimulate NKp30-mediated cytolytic activity for tumor immunotherapy.
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spelling pubmed-31353532011-10-11 Structure of the human activating natural cytotoxicity receptor NKp30 bound to its tumor cell ligand B7-H6 Li, Yili Wang, Qian Mariuzza, Roy A. J Exp Med Article Natural killer (NK) cells are lymphocytes of the innate immune system that participate in the elimination of tumor cells. In humans, the activating natural cytotoxicity receptors (NCRs) NKp30, NKp44, and NKp46 play a major role in NK cell–mediated tumor cell lysis. NKp30 recognizes B7-H6, a member of the B7 family which is expressed on tumor, but not healthy, cells. To understand the basis for tumor surveillance by NCRs, we determined the structure of NKp30, a member of the CD28 family which includes CTLA-4 and PD-1, in complex with B7-H6. The overall organization of the NKp30–B7-H6–activating complex differs considerably from those of the CTLA-4–B7 and PD-1–PD-L T cell inhibitory complexes. Whereas CTLA-4 and PD-1 use only the front β-sheet of their Ig-like domain to bind ligands, NKp30 uses both front and back β-sheets, resulting in engagement of B7-H6 via the side, as well as face, of the β-sandwich. Moreover, B7-H6 contacts NKp30 through the complementarity-determining region (CDR)–like loops of its V-like domain in an antibody-like interaction that is not observed for B7 or PD-L. This first structure of an NCR bound to ligand provides a template for designing molecules to stimulate NKp30-mediated cytolytic activity for tumor immunotherapy. The Rockefeller University Press 2011-04-11 /pmc/articles/PMC3135353/ /pubmed/21422170 http://dx.doi.org/10.1084/jem.20102548 Text en © 2011 Li et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Li, Yili
Wang, Qian
Mariuzza, Roy A.
Structure of the human activating natural cytotoxicity receptor NKp30 bound to its tumor cell ligand B7-H6
title Structure of the human activating natural cytotoxicity receptor NKp30 bound to its tumor cell ligand B7-H6
title_full Structure of the human activating natural cytotoxicity receptor NKp30 bound to its tumor cell ligand B7-H6
title_fullStr Structure of the human activating natural cytotoxicity receptor NKp30 bound to its tumor cell ligand B7-H6
title_full_unstemmed Structure of the human activating natural cytotoxicity receptor NKp30 bound to its tumor cell ligand B7-H6
title_short Structure of the human activating natural cytotoxicity receptor NKp30 bound to its tumor cell ligand B7-H6
title_sort structure of the human activating natural cytotoxicity receptor nkp30 bound to its tumor cell ligand b7-h6
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135353/
https://www.ncbi.nlm.nih.gov/pubmed/21422170
http://dx.doi.org/10.1084/jem.20102548
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