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Host KIR/HLA-C Genotypes Determine HIV-Mediated Changes of the NK Cell Repertoire and Are Associated With Vpu Sequence Variations Impacting Downmodulation of HLA-C

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Host KIR/HLA-C Genotypes Determine HIV-Mediated Changes of the NK Cell Repertoire and Are Associated With Vpu Sequence Variations Impacting Downmodulation of HLA-C. / Vollmers, Sarah; Lobermeyer, Annabelle; Niehrs, Annika; Fittje, Pia; Indenbirken, Daniela; Nakel, Jacqueline; Virdi, Sanamjeet; Brias, Sebastien; Trenkner, Timo; Sauer, Gabriel; Peine, Sven; Behrens, Georg M N; Lehmann, Clara; Meurer, Anja; Pauli, Ramona; Postel, Nils; Roider, Julia; Scholten, Stefan; Spinner, Christoph D; Stephan, Christoph; Wolf, Eva; Wyen, Christoph; Richert, Laura; Norman, Paul J; Sauter, Jürgen; Schmidt, Alexander H; Hölzemer, Angelique; Altfeld, Marcus; Körner, Christian.

In: FRONT IMMUNOL, Vol. 13, 922252, 2022.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Vollmers, S, Lobermeyer, A, Niehrs, A, Fittje, P, Indenbirken, D, Nakel, J, Virdi, S, Brias, S, Trenkner, T, Sauer, G, Peine, S, Behrens, GMN, Lehmann, C, Meurer, A, Pauli, R, Postel, N, Roider, J, Scholten, S, Spinner, CD, Stephan, C, Wolf, E, Wyen, C, Richert, L, Norman, PJ, Sauter, J, Schmidt, AH, Hölzemer, A, Altfeld, M & Körner, C 2022, 'Host KIR/HLA-C Genotypes Determine HIV-Mediated Changes of the NK Cell Repertoire and Are Associated With Vpu Sequence Variations Impacting Downmodulation of HLA-C', FRONT IMMUNOL, vol. 13, 922252. https://doi.org/10.3389/fimmu.2022.922252

APA

Vollmers, S., Lobermeyer, A., Niehrs, A., Fittje, P., Indenbirken, D., Nakel, J., Virdi, S., Brias, S., Trenkner, T., Sauer, G., Peine, S., Behrens, G. M. N., Lehmann, C., Meurer, A., Pauli, R., Postel, N., Roider, J., Scholten, S., Spinner, C. D., ... Körner, C. (2022). Host KIR/HLA-C Genotypes Determine HIV-Mediated Changes of the NK Cell Repertoire and Are Associated With Vpu Sequence Variations Impacting Downmodulation of HLA-C. FRONT IMMUNOL, 13, [922252]. https://doi.org/10.3389/fimmu.2022.922252

Vancouver

Vollmers S, Lobermeyer A, Niehrs A, Fittje P, Indenbirken D, Nakel J et al. Host KIR/HLA-C Genotypes Determine HIV-Mediated Changes of the NK Cell Repertoire and Are Associated With Vpu Sequence Variations Impacting Downmodulation of HLA-C. FRONT IMMUNOL. 2022;13. 922252. https://doi.org/10.3389/fimmu.2022.922252

Bibtex

@article{2a45d4c3d97c46d087b8db720881eaad,
title = "Host KIR/HLA-C Genotypes Determine HIV-Mediated Changes of the NK Cell Repertoire and Are Associated With Vpu Sequence Variations Impacting Downmodulation of HLA-C",
abstract = "NK cells play a pivotal role in viral immunity, utilizing a large array of activating and inhibitory receptors to identify and eliminate virus-infected cells. Killer-cell immunoglobulin-like receptors (KIRs) represent a highly polymorphic receptor family, regulating NK cell activity and determining the ability to recognize target cells. Human leukocyte antigen (HLA) class I molecules serve as the primary ligand for KIRs. Herein, HLA-C stands out as being the dominant ligand for the majority of KIRs. Accumulating evidence indicated that interactions between HLA-C and its inhibitory KIR2DL receptors (KIR2DL1/L2/L3) can drive HIV-1-mediated immune evasion and thus may contribute to the intrinsic control of HIV-1 infection. Of particular interest in this context is the recent observation that HIV-1 is able to adapt to host HLA-C genotypes through Vpu-mediated downmodulation of HLA-C. However, our understanding of the complex interplay between KIR/HLA immunogenetics, NK cell-mediated immune pressure and HIV-1 immune escape is still limited. Therefore, we investigated the impact of specific KIR/HLA-C combinations on the NK cell receptor repertoire and HIV-1 Vpu protein sequence variations of 122 viremic, untreated HIV-1+ individuals. Compared to 60 HIV-1- controls, HIV-1 infection was associated with significant changes within the NK cell receptor repertoire, including reduced percentages of NK cells expressing NKG2A, CD8, and KIR2DS4. In contrast, the NKG2C+ and KIR3DL2+ NK cell sub-populations from HIV-1+ individuals was enlarged compared to HIV-1- controls. Stratification along KIR/HLA-C genotypes revealed a genotype-dependent expansion of KIR2DL1+ NK cells that was ultimately associated with increased binding affinities between KIR2DL1 and HLA-C allotypes. Lastly, our data hinted to a preferential selection of Vpu sequence variants that were associated with HLA-C downmodulation in individuals with high KIR2DL/HLA-C binding affinities. Altogether, our study provides evidence that HIV-1-associated changes in the KIR repertoire of NK cells are to some extent predetermined by host KIR2DL/HLA-C genotypes. Furthermore, analysis of Vpu sequence polymorphisms indicates that differential KIR2DL/HLA-C binding affinities may serve as an additional mechanism how host genetics impact immune evasion by HIV-1.",
keywords = "Genotype, HIV Infections, HIV-1, HLA-C Antigens/metabolism, Histocompatibility Antigens Class I/genetics, Human Immunodeficiency Virus Proteins/genetics, Humans, Killer Cells, Natural, Ligands, Receptors, KIR/metabolism, Receptors, Natural Killer Cell/metabolism, Viral Regulatory and Accessory Proteins/metabolism, Viroporin Proteins",
author = "Sarah Vollmers and Annabelle Lobermeyer and Annika Niehrs and Pia Fittje and Daniela Indenbirken and Jacqueline Nakel and Sanamjeet Virdi and Sebastien Brias and Timo Trenkner and Gabriel Sauer and Sven Peine and Behrens, {Georg M N} and Clara Lehmann and Anja Meurer and Ramona Pauli and Nils Postel and Julia Roider and Stefan Scholten and Spinner, {Christoph D} and Christoph Stephan and Eva Wolf and Christoph Wyen and Laura Richert and Norman, {Paul J} and J{\"u}rgen Sauter and Schmidt, {Alexander H} and Angelique H{\"o}lzemer and Marcus Altfeld and Christian K{\"o}rner",
note = "Copyright {\textcopyright} 2022 Vollmers, Lobermeyer, Niehrs, Fittje, Indenbirken, Nakel, Virdi, Brias, Trenkner, Sauer, Peine, Behrens, Lehmann, Meurer, Pauli, Postel, Roider, Scholten, Spinner, Stephan, Wolf, Wyen, Richert, Norman, Sauter, Schmidt, Hoelzemer, Altfeld and K{\"o}rner.",
year = "2022",
doi = "10.3389/fimmu.2022.922252",
language = "English",
volume = "13",
journal = "FRONT IMMUNOL",
issn = "1664-3224",
publisher = "Lausanne : Frontiers Research Foundation",

}

RIS

TY - JOUR

T1 - Host KIR/HLA-C Genotypes Determine HIV-Mediated Changes of the NK Cell Repertoire and Are Associated With Vpu Sequence Variations Impacting Downmodulation of HLA-C

AU - Vollmers, Sarah

AU - Lobermeyer, Annabelle

AU - Niehrs, Annika

AU - Fittje, Pia

AU - Indenbirken, Daniela

AU - Nakel, Jacqueline

AU - Virdi, Sanamjeet

AU - Brias, Sebastien

AU - Trenkner, Timo

AU - Sauer, Gabriel

AU - Peine, Sven

AU - Behrens, Georg M N

AU - Lehmann, Clara

AU - Meurer, Anja

AU - Pauli, Ramona

AU - Postel, Nils

AU - Roider, Julia

AU - Scholten, Stefan

AU - Spinner, Christoph D

AU - Stephan, Christoph

AU - Wolf, Eva

AU - Wyen, Christoph

AU - Richert, Laura

AU - Norman, Paul J

AU - Sauter, Jürgen

AU - Schmidt, Alexander H

AU - Hölzemer, Angelique

AU - Altfeld, Marcus

AU - Körner, Christian

N1 - Copyright © 2022 Vollmers, Lobermeyer, Niehrs, Fittje, Indenbirken, Nakel, Virdi, Brias, Trenkner, Sauer, Peine, Behrens, Lehmann, Meurer, Pauli, Postel, Roider, Scholten, Spinner, Stephan, Wolf, Wyen, Richert, Norman, Sauter, Schmidt, Hoelzemer, Altfeld and Körner.

PY - 2022

Y1 - 2022

N2 - NK cells play a pivotal role in viral immunity, utilizing a large array of activating and inhibitory receptors to identify and eliminate virus-infected cells. Killer-cell immunoglobulin-like receptors (KIRs) represent a highly polymorphic receptor family, regulating NK cell activity and determining the ability to recognize target cells. Human leukocyte antigen (HLA) class I molecules serve as the primary ligand for KIRs. Herein, HLA-C stands out as being the dominant ligand for the majority of KIRs. Accumulating evidence indicated that interactions between HLA-C and its inhibitory KIR2DL receptors (KIR2DL1/L2/L3) can drive HIV-1-mediated immune evasion and thus may contribute to the intrinsic control of HIV-1 infection. Of particular interest in this context is the recent observation that HIV-1 is able to adapt to host HLA-C genotypes through Vpu-mediated downmodulation of HLA-C. However, our understanding of the complex interplay between KIR/HLA immunogenetics, NK cell-mediated immune pressure and HIV-1 immune escape is still limited. Therefore, we investigated the impact of specific KIR/HLA-C combinations on the NK cell receptor repertoire and HIV-1 Vpu protein sequence variations of 122 viremic, untreated HIV-1+ individuals. Compared to 60 HIV-1- controls, HIV-1 infection was associated with significant changes within the NK cell receptor repertoire, including reduced percentages of NK cells expressing NKG2A, CD8, and KIR2DS4. In contrast, the NKG2C+ and KIR3DL2+ NK cell sub-populations from HIV-1+ individuals was enlarged compared to HIV-1- controls. Stratification along KIR/HLA-C genotypes revealed a genotype-dependent expansion of KIR2DL1+ NK cells that was ultimately associated with increased binding affinities between KIR2DL1 and HLA-C allotypes. Lastly, our data hinted to a preferential selection of Vpu sequence variants that were associated with HLA-C downmodulation in individuals with high KIR2DL/HLA-C binding affinities. Altogether, our study provides evidence that HIV-1-associated changes in the KIR repertoire of NK cells are to some extent predetermined by host KIR2DL/HLA-C genotypes. Furthermore, analysis of Vpu sequence polymorphisms indicates that differential KIR2DL/HLA-C binding affinities may serve as an additional mechanism how host genetics impact immune evasion by HIV-1.

AB - NK cells play a pivotal role in viral immunity, utilizing a large array of activating and inhibitory receptors to identify and eliminate virus-infected cells. Killer-cell immunoglobulin-like receptors (KIRs) represent a highly polymorphic receptor family, regulating NK cell activity and determining the ability to recognize target cells. Human leukocyte antigen (HLA) class I molecules serve as the primary ligand for KIRs. Herein, HLA-C stands out as being the dominant ligand for the majority of KIRs. Accumulating evidence indicated that interactions between HLA-C and its inhibitory KIR2DL receptors (KIR2DL1/L2/L3) can drive HIV-1-mediated immune evasion and thus may contribute to the intrinsic control of HIV-1 infection. Of particular interest in this context is the recent observation that HIV-1 is able to adapt to host HLA-C genotypes through Vpu-mediated downmodulation of HLA-C. However, our understanding of the complex interplay between KIR/HLA immunogenetics, NK cell-mediated immune pressure and HIV-1 immune escape is still limited. Therefore, we investigated the impact of specific KIR/HLA-C combinations on the NK cell receptor repertoire and HIV-1 Vpu protein sequence variations of 122 viremic, untreated HIV-1+ individuals. Compared to 60 HIV-1- controls, HIV-1 infection was associated with significant changes within the NK cell receptor repertoire, including reduced percentages of NK cells expressing NKG2A, CD8, and KIR2DS4. In contrast, the NKG2C+ and KIR3DL2+ NK cell sub-populations from HIV-1+ individuals was enlarged compared to HIV-1- controls. Stratification along KIR/HLA-C genotypes revealed a genotype-dependent expansion of KIR2DL1+ NK cells that was ultimately associated with increased binding affinities between KIR2DL1 and HLA-C allotypes. Lastly, our data hinted to a preferential selection of Vpu sequence variants that were associated with HLA-C downmodulation in individuals with high KIR2DL/HLA-C binding affinities. Altogether, our study provides evidence that HIV-1-associated changes in the KIR repertoire of NK cells are to some extent predetermined by host KIR2DL/HLA-C genotypes. Furthermore, analysis of Vpu sequence polymorphisms indicates that differential KIR2DL/HLA-C binding affinities may serve as an additional mechanism how host genetics impact immune evasion by HIV-1.

KW - Genotype

KW - HIV Infections

KW - HIV-1

KW - HLA-C Antigens/metabolism

KW - Histocompatibility Antigens Class I/genetics

KW - Human Immunodeficiency Virus Proteins/genetics

KW - Humans

KW - Killer Cells, Natural

KW - Ligands

KW - Receptors, KIR/metabolism

KW - Receptors, Natural Killer Cell/metabolism

KW - Viral Regulatory and Accessory Proteins/metabolism

KW - Viroporin Proteins

U2 - 10.3389/fimmu.2022.922252

DO - 10.3389/fimmu.2022.922252

M3 - SCORING: Journal article

C2 - 35911762

VL - 13

JO - FRONT IMMUNOL

JF - FRONT IMMUNOL

SN - 1664-3224

M1 - 922252

ER -