A CMV-induced adaptive human Vδ1+ γδ T cell clone recognizes HLA-DR

Malte Deseke; Francesca Rampoldi; Inga Sandrock; Eva Borst; Heike Böning; George Liam Ssebyatika; Carina Jürgens; Nina Plückebaum; Maleen Beck; Ahmed Hassan; Likai Tan; Abdi Demera; Anika Janssen; Peter Steinberger; Christian Koenecke; Abel Viejo-Borbolla; Martin Messerle; Thomas Krey; Immo Prinz

doi:10.1084/jem.20212525

A CMV-induced adaptive human Vδ1⁺ γδ T cell clone recognizes HLA-DR

Malte Deseke, Francesca Rampoldi, Inga Sandrock, Eva Borst, Heike Böning, George Liam Ssebyatika, Carina Jürgens, Nina Plückebaum, Maleen Beck, Ahmed Hassan, Likai Tan, Abdi Demera, Anika Janssen, Peter Steinberger, Christian Koenecke, Abel Viejo-Borbolla, Martin Messerle, Thomas Krey, Immo Prinz^*

^*Corresponding author for this work

Institute of Biochemistry

46 Citations (Scopus)

Abstract

The innate and adaptive roles of γδ T cells and their clonal γδ T cell receptors (TCRs) in immune responses are still unclear. Recent studies of γδ TCR repertoire dynamics showed massive expansion of individual Vδ1⁺ γδ T cell clones during viral infection. To judge whether such expansion is random or actually represents TCR-dependent adaptive immune responses, information about their cognate TCR ligands is required. Here, we used CRISPR/Cas9-mediated screening to identify HLA-DRA, RFXAP, RFX5, and CIITA as required for target cell recognition of a CMV-induced Vγ3Vδ1⁺ TCR, and further characterization revealed a direct interaction of this Vδ1⁺ TCR with the MHC II complex HLA-DR. Since MHC II is strongly upregulated by interferon-γ, these results suggest an inflammation-induced MHC-dependent immune response of γδ T cells.

Original language	English
Article number	e20212525
Journal	Journal of Experimental Medicine
Volume	219
Issue number	9
ISSN	0022-1007
DOIs	https://doi.org/10.1084/jem.20212525
Publication status	Published - 05.09.2022

Funding

This work was supported by the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation) Research Unit FOR 2799 to I. Prinz (Project PR727/11-1) and T. Krey; grant CRC SFB900 (Project ID 158989968) to C. Koenecke and I. Prinz; and under Germany’s Excellence Strategy (EXC 2155 “RESIST”), Project ID 390874280 to A.V. Borbolla, M. Messerle, T. Krey, and I. Prinz. M. Deseke, G.L. Ssebyatika, C. Jürgens, N. Plückebaum, and A. Hassan were supported by the Hannover Biomedical Research School and Zentrum für Infektionsbiologie; C. Jürgens was supported by a DFG grant from the DFG, VI 762/1-1, Project ID 405772731. We thank M. Ballmeier for support from the cell-sorting core facility of Hannover Medical School. Furthermore, we thank B. Bosnjak for providing scientific and technical advice for the generation of CRISPR/Cas9 knockout cell lines and gene repair experiments. We also thank A. Fichtner, E. Bruni, and M. Stieger for helping with the isolation of PBMCs.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)
Centers: Center for Structural and Cell Biology (CSCM/ZMSZ)

Access to Document

10.1084/jem.20212525

Cite this

Deseke, M., Rampoldi, F., Sandrock, I., Borst, E., Böning, H., Ssebyatika, G. L., Jürgens, C., Plückebaum, N., Beck, M., Hassan, A., Tan, L., Demera, A., Janssen, A., Steinberger, P., Koenecke, C., Viejo-Borbolla, A., Messerle, M., Krey, T., & Prinz, I. (2022). A CMV-induced adaptive human Vδ1⁺ γδ T cell clone recognizes HLA-DR. Journal of Experimental Medicine, 219(9), Article e20212525. https://doi.org/10.1084/jem.20212525

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abstract = "The innate and adaptive roles of γδ T cells and their clonal γδ T cell receptors (TCRs) in immune responses are still unclear. Recent studies of γδ TCR repertoire dynamics showed massive expansion of individual Vδ1+ γδ T cell clones during viral infection. To judge whether such expansion is random or actually represents TCR-dependent adaptive immune responses, information about their cognate TCR ligands is required. Here, we used CRISPR/Cas9-mediated screening to identify HLA-DRA, RFXAP, RFX5, and CIITA as required for target cell recognition of a CMV-induced Vγ3Vδ1+ TCR, and further characterization revealed a direct interaction of this Vδ1+ TCR with the MHC II complex HLA-DR. Since MHC II is strongly upregulated by interferon-γ, these results suggest an inflammation-induced MHC-dependent immune response of γδ T cells.",

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Deseke, M, Rampoldi, F, Sandrock, I, Borst, E, Böning, H, Ssebyatika, GL, Jürgens, C, Plückebaum, N, Beck, M, Hassan, A, Tan, L, Demera, A, Janssen, A, Steinberger, P, Koenecke, C, Viejo-Borbolla, A, Messerle, M, Krey, T & Prinz, I 2022, 'A CMV-induced adaptive human Vδ1⁺ γδ T cell clone recognizes HLA-DR', Journal of Experimental Medicine, vol. 219, no. 9, e20212525. https://doi.org/10.1084/jem.20212525

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AU - Böning, Heike

AU - Ssebyatika, George Liam

AU - Jürgens, Carina

AU - Plückebaum, Nina

AU - Beck, Maleen

AU - Hassan, Ahmed

AU - Tan, Likai

AU - Demera, Abdi

AU - Janssen, Anika

AU - Steinberger, Peter

AU - Koenecke, Christian

AU - Viejo-Borbolla, Abel

AU - Messerle, Martin

AU - Krey, Thomas

AU - Prinz, Immo

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AB - The innate and adaptive roles of γδ T cells and their clonal γδ T cell receptors (TCRs) in immune responses are still unclear. Recent studies of γδ TCR repertoire dynamics showed massive expansion of individual Vδ1+ γδ T cell clones during viral infection. To judge whether such expansion is random or actually represents TCR-dependent adaptive immune responses, information about their cognate TCR ligands is required. Here, we used CRISPR/Cas9-mediated screening to identify HLA-DRA, RFXAP, RFX5, and CIITA as required for target cell recognition of a CMV-induced Vγ3Vδ1+ TCR, and further characterization revealed a direct interaction of this Vδ1+ TCR with the MHC II complex HLA-DR. Since MHC II is strongly upregulated by interferon-γ, these results suggest an inflammation-induced MHC-dependent immune response of γδ T cells.

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