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Molecular Competition for NKG2D: H60 and RAE1 Compete Unequally for NKG2D with Dominance of H60

O'Callaghan, Christopher A. and Cerwenka, Adelheid and Willcox, Benjamin E. and Lanier, Lewis L. and Bjorkman, Pamela J. (2001) Molecular Competition for NKG2D: H60 and RAE1 Compete Unequally for NKG2D with Dominance of H60. Immunity, 15 (2). pp. 201-211. ISSN 1074-7613. https://resolver.caltech.edu/CaltechAUTHORS:20170327-131126216

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Abstract

NKG2D is a potent activating receptor on natural killer cells, T cells, and macrophages. Mouse NKG2D interacts with two cell surface ligands related to class I MHC molecules: RAE1 and H60. We used soluble versions of NKG2D, RAE1, and H60 to characterize their interactions. RAE1 and H60 each bind NKG2D with nanomolar affinities, indicating tighter binding than most cell surface immune interactions, but NKG2D binds to H60 with ∼25-fold higher affinity than to RAE1. RAE1 and H60 compete directly for occupancy of NKG2D, and, thus, NKG2D can be occupied by only one ligand at a time. The NKG2D-H60 interaction is more temperature dependent and makes greater use of electrostatic interactions than the NKG2D-RAE1 interaction. The distinct thermodynamic profiles provide insights into the different molecular mechanisms of the binding interactions.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/S1074-7613(01)00187-XDOIArticle
http://www.sciencedirect.com/science/article/pii/S107476130100187XPublisherArticle
ORCID:
AuthorORCID
Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 2001 Cell Press. Received 1 May 2001, Revised 21 June 2001, Available online 27 August 2001. C.A.O'C. is an MRC Fellow. B.E.W. is a Wellcome Trust Fellow. A.C. and L.L.L. are supported by NIH grant CA 89189. We are grateful to Roland Strong and members of the Bjorkman and Lanier labs for helpful discussions and critical reading of the manuscript and to Sandy Zurawski for the original Ig-fusion constructs.
Funders:
Funding AgencyGrant Number
Medical Research Council (UK)UNSPECIFIED
Wellcome TrustUNSPECIFIED
NIHCA 89189
Issue or Number:2
Record Number:CaltechAUTHORS:20170327-131126216
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170327-131126216
Official Citation:Christopher A O'Callaghan, Adelheid Cerwenka, Benjamin E Willcox, Lewis L Lanier, Pamela J Bjorkman, Molecular Competition for NKG2D: H60 and RAE1 Compete Unequally for NKG2D with Dominance of H60, Immunity, Volume 15, Issue 2, August 2001, Pages 201-211, ISSN 1074-7613, http://dx.doi.org/10.1016/S1074-7613(01)00187-X. (http://www.sciencedirect.com/science/article/pii/S107476130100187X)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:75421
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:27 Mar 2017 20:25
Last Modified:03 Oct 2019 16:50

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