A subset of HLA-DP molecules serve as ligands for the natural cytotoxicity receptor NKp44

Annika Niehrs, Wilfredo F. Garcia-Beltran, Paul J. Norman, Gabrielle M. Watson, Angelique Hölzemer, Anaïs Chapel, Laura Richert, Andreas Pommerening-Röser, Christian Körner, Mikki Ozawa, Glòria Martrus, Jamie Rossjohn, Jar-How Lee, Richard Berry, Mary Carrington, Marcus Altfeld

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

Natural killer (NK) cells can recognize virus-infected and stressed cells1 using activating and inhibitory receptors, many of which interact with HLA class I. Although early studies also suggested a functional impact of HLA class II on NK cell activity2,3, the NK cell receptors that specifically recognize HLA class II molecules have never been identified. We investigated whether two major families of NK cell receptors, killer-cell immunoglobulin-like receptors (KIRs) and natural cytotoxicity receptors (NCRs), contained receptors that bound to HLA class II, and identified a direct interaction between the NK cell receptor NKp44 and a subset of HLA-DP molecules, including HLA-DP401, one of the most frequent class II allotypes in white populations4. Using NKp44ζ+ reporter cells and primary human NKp44+ NK cells, we demonstrated that interactions between NKp44 and HLA-DP401 trigger functional NK cell responses. This interaction between a subset of HLA-DP molecules and NKp44 implicates HLA class II as a component of the innate immune response, much like HLA class I. It also provides a potential mechanism for the described associations between HLA-DP subtypes and several disease outcomes, including hepatitis B virus infection5,6,7, graft-versus-host disease8 and inflammatory bowel disease9,10.
Original languageEnglish
Pages (from-to)1129-1137
Number of pages9
JournalNature Immunology
Volume20
Issue number9
DOIs
Publication statusPublished - 29 Jul 2019

Keywords

  • innate immune cells
  • NK cells

Cite this

Niehrs, A., Garcia-Beltran, W. F., Norman, P. J., Watson, G. M., Hölzemer, A., Chapel, A., ... Altfeld, M. (2019). A subset of HLA-DP molecules serve as ligands for the natural cytotoxicity receptor NKp44. Nature Immunology, 20(9), 1129-1137. https://doi.org/10.1038/s41590-019-0448-4
Niehrs, Annika ; Garcia-Beltran, Wilfredo F. ; Norman, Paul J. ; Watson, Gabrielle M. ; Hölzemer, Angelique ; Chapel, Anaïs ; Richert, Laura ; Pommerening-Röser, Andreas ; Körner, Christian ; Ozawa, Mikki ; Martrus, Glòria ; Rossjohn, Jamie ; Lee, Jar-How ; Berry, Richard ; Carrington, Mary ; Altfeld, Marcus. / A subset of HLA-DP molecules serve as ligands for the natural cytotoxicity receptor NKp44. In: Nature Immunology. 2019 ; Vol. 20, No. 9. pp. 1129-1137.
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abstract = "Natural killer (NK) cells can recognize virus-infected and stressed cells1 using activating and inhibitory receptors, many of which interact with HLA class I. Although early studies also suggested a functional impact of HLA class II on NK cell activity2,3, the NK cell receptors that specifically recognize HLA class II molecules have never been identified. We investigated whether two major families of NK cell receptors, killer-cell immunoglobulin-like receptors (KIRs) and natural cytotoxicity receptors (NCRs), contained receptors that bound to HLA class II, and identified a direct interaction between the NK cell receptor NKp44 and a subset of HLA-DP molecules, including HLA-DP401, one of the most frequent class II allotypes in white populations4. Using NKp44ζ+ reporter cells and primary human NKp44+ NK cells, we demonstrated that interactions between NKp44 and HLA-DP401 trigger functional NK cell responses. This interaction between a subset of HLA-DP molecules and NKp44 implicates HLA class II as a component of the innate immune response, much like HLA class I. It also provides a potential mechanism for the described associations between HLA-DP subtypes and several disease outcomes, including hepatitis B virus infection5,6,7, graft-versus-host disease8 and inflammatory bowel disease9,10.",
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Niehrs, A, Garcia-Beltran, WF, Norman, PJ, Watson, GM, Hölzemer, A, Chapel, A, Richert, L, Pommerening-Röser, A, Körner, C, Ozawa, M, Martrus, G, Rossjohn, J, Lee, J-H, Berry, R, Carrington, M & Altfeld, M 2019, 'A subset of HLA-DP molecules serve as ligands for the natural cytotoxicity receptor NKp44', Nature Immunology, vol. 20, no. 9, pp. 1129-1137. https://doi.org/10.1038/s41590-019-0448-4

A subset of HLA-DP molecules serve as ligands for the natural cytotoxicity receptor NKp44. / Niehrs, Annika; Garcia-Beltran, Wilfredo F.; Norman, Paul J.; Watson, Gabrielle M.; Hölzemer, Angelique; Chapel, Anaïs; Richert, Laura; Pommerening-Röser, Andreas; Körner, Christian; Ozawa, Mikki; Martrus, Glòria; Rossjohn, Jamie; Lee, Jar-How; Berry, Richard; Carrington, Mary; Altfeld, Marcus.

In: Nature Immunology, Vol. 20, No. 9, 29.07.2019, p. 1129-1137.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Niehrs, Annika

AU - Garcia-Beltran, Wilfredo F.

AU - Norman, Paul J.

AU - Watson, Gabrielle M.

AU - Hölzemer, Angelique

AU - Chapel, Anaïs

AU - Richert, Laura

AU - Pommerening-Röser, Andreas

AU - Körner, Christian

AU - Ozawa, Mikki

AU - Martrus, Glòria

AU - Rossjohn, Jamie

AU - Lee, Jar-How

AU - Berry, Richard

AU - Carrington, Mary

AU - Altfeld, Marcus

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N2 - Natural killer (NK) cells can recognize virus-infected and stressed cells1 using activating and inhibitory receptors, many of which interact with HLA class I. Although early studies also suggested a functional impact of HLA class II on NK cell activity2,3, the NK cell receptors that specifically recognize HLA class II molecules have never been identified. We investigated whether two major families of NK cell receptors, killer-cell immunoglobulin-like receptors (KIRs) and natural cytotoxicity receptors (NCRs), contained receptors that bound to HLA class II, and identified a direct interaction between the NK cell receptor NKp44 and a subset of HLA-DP molecules, including HLA-DP401, one of the most frequent class II allotypes in white populations4. Using NKp44ζ+ reporter cells and primary human NKp44+ NK cells, we demonstrated that interactions between NKp44 and HLA-DP401 trigger functional NK cell responses. This interaction between a subset of HLA-DP molecules and NKp44 implicates HLA class II as a component of the innate immune response, much like HLA class I. It also provides a potential mechanism for the described associations between HLA-DP subtypes and several disease outcomes, including hepatitis B virus infection5,6,7, graft-versus-host disease8 and inflammatory bowel disease9,10.

AB - Natural killer (NK) cells can recognize virus-infected and stressed cells1 using activating and inhibitory receptors, many of which interact with HLA class I. Although early studies also suggested a functional impact of HLA class II on NK cell activity2,3, the NK cell receptors that specifically recognize HLA class II molecules have never been identified. We investigated whether two major families of NK cell receptors, killer-cell immunoglobulin-like receptors (KIRs) and natural cytotoxicity receptors (NCRs), contained receptors that bound to HLA class II, and identified a direct interaction between the NK cell receptor NKp44 and a subset of HLA-DP molecules, including HLA-DP401, one of the most frequent class II allotypes in white populations4. Using NKp44ζ+ reporter cells and primary human NKp44+ NK cells, we demonstrated that interactions between NKp44 and HLA-DP401 trigger functional NK cell responses. This interaction between a subset of HLA-DP molecules and NKp44 implicates HLA class II as a component of the innate immune response, much like HLA class I. It also provides a potential mechanism for the described associations between HLA-DP subtypes and several disease outcomes, including hepatitis B virus infection5,6,7, graft-versus-host disease8 and inflammatory bowel disease9,10.

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