Recognition of the nonclassical MHC class i molecule H2-M3 by the receptor Ly49A regulates the licensing and activation of NK cells

Daniel M. Andrews; Lucy C. Sullivan; Nikola Baschuk; Christopher J. Chan; Richard Berry; Claire L. Cotterell; Jie Lin; Heloise Halse; Sally V. Watt; Jennifer Poursine-Laurent; Chyung Ru Wang; Anthony A. Scalzo; Wayne M. Yokoyama; Jamie Rossjohn; Andrew G. Brooks; Mark J. Smyth

doi:10.1038/ni.2468

Recognition of the nonclassical MHC class i molecule H2-M3 by the receptor Ly49A regulates the licensing and activation of NK cells

Daniel M. Andrews^*, Lucy C. Sullivan, Nikola Baschuk, Christopher J. Chan, Richard Berry, Claire L. Cotterell, Jie Lin, Heloise Halse, Sally V. Watt, Jennifer Poursine-Laurent, Chyung Ru Wang, Anthony A. Scalzo, Wayne M. Yokoyama, Jamie Rossjohn, Andrew G. Brooks, Mark J. Smyth

^*Corresponding author for this work

Microbiology-Immunology

Research output: Contribution to journal › Article › peer-review

46 Scopus citations

Abstract

The development and function of natural killer (NK) cells is regulated by the interaction of inhibitory receptors of the Ly49 family with distinct peptide-laden major histocompatibility complex (MHC) class I molecules, although whether the Ly49 family is able bind to other MHC class I-like molecules is unclear. Here we found that the prototypic inhibitory receptor Ly49A bound the highly conserved nonclassical MHC class I molecule H2-M3 with an affinity similar to its affinity for H-2D d. The specific recognition of H2-M3 by Ly49A regulated the 'licensing' of NK cells and mediated 'missing-self' recognition of H2-M3-deficient bone marrow. Host peptide-H2-M3 was required for optimal NK cell activity against experimental metastases and carcinogenesis. Thus, nonclassical MHC class I molecules can act as cognate ligands for Ly49 molecules. Our results provide insight into the various mechanisms that lead to NK cell tolerance.

Original language	English (US)
Pages (from-to)	1171-1177
Number of pages	7
Journal	Nature Immunology
Volume	13
Issue number	12
DOIs	https://doi.org/10.1038/ni.2468
State	Published - Dec 2012

Funding

We thank C. Paget for critical analysis of the manuscript; E. Hawkins, Q. Mundrea, B. Venville, N. McLaughlin and J. Sharkey for technical assistance; and B. Murphy (UC Davis Cancer Center) for the YE1/32 antibody to Ly49A. Supported by the National Health and Medical Research Council of Australia (D.M.A., L.C.S., R.B., M.J.S., A.G.B. and J.R.), Cancer Australia, the Cure Cancer Australia Foundation, the US National Institutes of Health (AI040310 to C.-R.W.) and the Howard Hughes Medical Institute (W.M.Y.).

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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Andrews, D. M., Sullivan, L. C., Baschuk, N., Chan, C. J., Berry, R., Cotterell, C. L., Lin, J., Halse, H., Watt, S. V., Poursine-Laurent, J., Wang, C. R., Scalzo, A. A., Yokoyama, W. M., Rossjohn, J., Brooks, A. G., & Smyth, M. J. (2012). Recognition of the nonclassical MHC class i molecule H2-M3 by the receptor Ly49A regulates the licensing and activation of NK cells. Nature Immunology, 13(12), 1171-1177. https://doi.org/10.1038/ni.2468

@article{bb70c5b9c93642a48382ceac541d78be,

title = "Recognition of the nonclassical MHC class i molecule H2-M3 by the receptor Ly49A regulates the licensing and activation of NK cells",

abstract = "The development and function of natural killer (NK) cells is regulated by the interaction of inhibitory receptors of the Ly49 family with distinct peptide-laden major histocompatibility complex (MHC) class I molecules, although whether the Ly49 family is able bind to other MHC class I-like molecules is unclear. Here we found that the prototypic inhibitory receptor Ly49A bound the highly conserved nonclassical MHC class I molecule H2-M3 with an affinity similar to its affinity for H-2D d. The specific recognition of H2-M3 by Ly49A regulated the 'licensing' of NK cells and mediated 'missing-self' recognition of H2-M3-deficient bone marrow. Host peptide-H2-M3 was required for optimal NK cell activity against experimental metastases and carcinogenesis. Thus, nonclassical MHC class I molecules can act as cognate ligands for Ly49 molecules. Our results provide insight into the various mechanisms that lead to NK cell tolerance.",

author = "Andrews, {Daniel M.} and Sullivan, {Lucy C.} and Nikola Baschuk and Chan, {Christopher J.} and Richard Berry and Cotterell, {Claire L.} and Jie Lin and Heloise Halse and Watt, {Sally V.} and Jennifer Poursine-Laurent and Wang, {Chyung Ru} and Scalzo, {Anthony A.} and Yokoyama, {Wayne M.} and Jamie Rossjohn and Brooks, {Andrew G.} and Smyth, {Mark J.}",

note = "Funding Information: We thank C. Paget for critical analysis of the manuscript; E. Hawkins, Q. Mundrea, B. Venville, N. McLaughlin and J. Sharkey for technical assistance; and B. Murphy (UC Davis Cancer Center) for the YE1/32 antibody to Ly49A. Supported by the National Health and Medical Research Council of Australia (D.M.A., L.C.S., R.B., M.J.S., A.G.B. and J.R.), Cancer Australia, the Cure Cancer Australia Foundation, the US National Institutes of Health (AI040310 to C.-R.W.) and the Howard Hughes Medical Institute (W.M.Y.).",

year = "2012",

month = dec,

doi = "10.1038/ni.2468",

language = "English (US)",

volume = "13",

pages = "1171--1177",

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Andrews, DM, Sullivan, LC, Baschuk, N, Chan, CJ, Berry, R, Cotterell, CL, Lin, J, Halse, H, Watt, SV, Poursine-Laurent, J, Wang, CR, Scalzo, AA, Yokoyama, WM, Rossjohn, J, Brooks, AG & Smyth, MJ 2012, 'Recognition of the nonclassical MHC class i molecule H2-M3 by the receptor Ly49A regulates the licensing and activation of NK cells', Nature Immunology, vol. 13, no. 12, pp. 1171-1177. https://doi.org/10.1038/ni.2468

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AU - Andrews, Daniel M.

AU - Sullivan, Lucy C.

AU - Baschuk, Nikola

AU - Chan, Christopher J.

AU - Berry, Richard

AU - Cotterell, Claire L.

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AU - Halse, Heloise

AU - Watt, Sally V.

AU - Poursine-Laurent, Jennifer

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AU - Scalzo, Anthony A.

AU - Yokoyama, Wayne M.

AU - Rossjohn, Jamie

AU - Brooks, Andrew G.

AU - Smyth, Mark J.

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N2 - The development and function of natural killer (NK) cells is regulated by the interaction of inhibitory receptors of the Ly49 family with distinct peptide-laden major histocompatibility complex (MHC) class I molecules, although whether the Ly49 family is able bind to other MHC class I-like molecules is unclear. Here we found that the prototypic inhibitory receptor Ly49A bound the highly conserved nonclassical MHC class I molecule H2-M3 with an affinity similar to its affinity for H-2D d. The specific recognition of H2-M3 by Ly49A regulated the 'licensing' of NK cells and mediated 'missing-self' recognition of H2-M3-deficient bone marrow. Host peptide-H2-M3 was required for optimal NK cell activity against experimental metastases and carcinogenesis. Thus, nonclassical MHC class I molecules can act as cognate ligands for Ly49 molecules. Our results provide insight into the various mechanisms that lead to NK cell tolerance.

AB - The development and function of natural killer (NK) cells is regulated by the interaction of inhibitory receptors of the Ly49 family with distinct peptide-laden major histocompatibility complex (MHC) class I molecules, although whether the Ly49 family is able bind to other MHC class I-like molecules is unclear. Here we found that the prototypic inhibitory receptor Ly49A bound the highly conserved nonclassical MHC class I molecule H2-M3 with an affinity similar to its affinity for H-2D d. The specific recognition of H2-M3 by Ly49A regulated the 'licensing' of NK cells and mediated 'missing-self' recognition of H2-M3-deficient bone marrow. Host peptide-H2-M3 was required for optimal NK cell activity against experimental metastases and carcinogenesis. Thus, nonclassical MHC class I molecules can act as cognate ligands for Ly49 molecules. Our results provide insight into the various mechanisms that lead to NK cell tolerance.

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Recognition of the nonclassical MHC class i molecule H2-M3 by the receptor Ly49A regulates the licensing and activation of NK cells

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