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NKG2D signaling certifies effector CD8 T cells for memory formation

BACKGROUND: The development of memory responses is an evolutionary function of the adaptive immune system. We propose that for the immune system to populate the memory compartment with the best-suited CD8 T cells it utilizes a process of certification or molecular accreditation mediated through Natu...

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Autores principales: Perez, Cynthia, Prajapati, Kushal, Burke, Brianna, Plaza-Rojas, Lourdes, Zeleznik-Le, Nancy J., Guevara-Patino, Jose A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380053/
https://www.ncbi.nlm.nih.gov/pubmed/30777125
http://dx.doi.org/10.1186/s40425-019-0531-2
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author Perez, Cynthia
Prajapati, Kushal
Burke, Brianna
Plaza-Rojas, Lourdes
Zeleznik-Le, Nancy J.
Guevara-Patino, Jose A.
author_facet Perez, Cynthia
Prajapati, Kushal
Burke, Brianna
Plaza-Rojas, Lourdes
Zeleznik-Le, Nancy J.
Guevara-Patino, Jose A.
author_sort Perez, Cynthia
collection PubMed
description BACKGROUND: The development of memory responses is an evolutionary function of the adaptive immune system. We propose that for the immune system to populate the memory compartment with the best-suited CD8 T cells it utilizes a process of certification or molecular accreditation mediated through Natural Killer Group 2D (NKG2D). This process of certification assures that the memory compartment is filled with CD8 T cells that have demonstrated their ability to kill their cognate targets through a two-step process that utilizes T cell receptor (TCR) and NKG2D signaling. METHODS: One week after immunization with peptide-pulsed dendritic cells, NKG2D signaling was transiently blocked in vivo with a single injection of neutralizing antibodies. Under such conditions, we determined the importance of NKG2D signaling during the effector phase for memory formation without compromising NKG2D signaling at the memory phase. Both open (polyclonal) and closed (monoclonal) CD8 T cell repertoires were studied. RESULTS: We show that signaling through NKG2D mediated this certification. Temporary blockade of NKG2D signaling during the effector phase resulted in the formation of highly defective memory CD8 T cells characterized by altered expression of the ribosomal protein S6 and epigenetic modifiers, suggesting modifications in the T cell translational machinery and epigenetic programming. Finally, these uncertified memory cells were not protective against a B16 tumor challenge. CONCLUSION: Signaling through NKG2D during the effector phase (certification) favors the development of functional memory CD8 T cells, a previously undescribed role for NKG2D. Temporary blockade of NKG2D signaling during the effector phase results in the formation of highly defective memory CD8 T cells potentially by affecting the expression of the ribosomal protein S6 and epigenetic modifiers, suggesting alterations in T cell translational machinery and epigenetic programming. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40425-019-0531-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-63800532019-02-28 NKG2D signaling certifies effector CD8 T cells for memory formation Perez, Cynthia Prajapati, Kushal Burke, Brianna Plaza-Rojas, Lourdes Zeleznik-Le, Nancy J. Guevara-Patino, Jose A. J Immunother Cancer Research Article BACKGROUND: The development of memory responses is an evolutionary function of the adaptive immune system. We propose that for the immune system to populate the memory compartment with the best-suited CD8 T cells it utilizes a process of certification or molecular accreditation mediated through Natural Killer Group 2D (NKG2D). This process of certification assures that the memory compartment is filled with CD8 T cells that have demonstrated their ability to kill their cognate targets through a two-step process that utilizes T cell receptor (TCR) and NKG2D signaling. METHODS: One week after immunization with peptide-pulsed dendritic cells, NKG2D signaling was transiently blocked in vivo with a single injection of neutralizing antibodies. Under such conditions, we determined the importance of NKG2D signaling during the effector phase for memory formation without compromising NKG2D signaling at the memory phase. Both open (polyclonal) and closed (monoclonal) CD8 T cell repertoires were studied. RESULTS: We show that signaling through NKG2D mediated this certification. Temporary blockade of NKG2D signaling during the effector phase resulted in the formation of highly defective memory CD8 T cells characterized by altered expression of the ribosomal protein S6 and epigenetic modifiers, suggesting modifications in the T cell translational machinery and epigenetic programming. Finally, these uncertified memory cells were not protective against a B16 tumor challenge. CONCLUSION: Signaling through NKG2D during the effector phase (certification) favors the development of functional memory CD8 T cells, a previously undescribed role for NKG2D. Temporary blockade of NKG2D signaling during the effector phase results in the formation of highly defective memory CD8 T cells potentially by affecting the expression of the ribosomal protein S6 and epigenetic modifiers, suggesting alterations in T cell translational machinery and epigenetic programming. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40425-019-0531-2) contains supplementary material, which is available to authorized users. BioMed Central 2019-02-18 /pmc/articles/PMC6380053/ /pubmed/30777125 http://dx.doi.org/10.1186/s40425-019-0531-2 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Perez, Cynthia
Prajapati, Kushal
Burke, Brianna
Plaza-Rojas, Lourdes
Zeleznik-Le, Nancy J.
Guevara-Patino, Jose A.
NKG2D signaling certifies effector CD8 T cells for memory formation
title NKG2D signaling certifies effector CD8 T cells for memory formation
title_full NKG2D signaling certifies effector CD8 T cells for memory formation
title_fullStr NKG2D signaling certifies effector CD8 T cells for memory formation
title_full_unstemmed NKG2D signaling certifies effector CD8 T cells for memory formation
title_short NKG2D signaling certifies effector CD8 T cells for memory formation
title_sort nkg2d signaling certifies effector cd8 t cells for memory formation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380053/
https://www.ncbi.nlm.nih.gov/pubmed/30777125
http://dx.doi.org/10.1186/s40425-019-0531-2
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