CD45RB Status of CD8+ T Cell Memory Defines T Cell Receptor Affinity and Persistence

Summary: The identity of CD45 isoforms on the T cell surface changes following the activation of naive T cells and impacts intracellular signaling. In this study, we find that the anti-viral memory CD8+ T pool is unexpectedly comprised of both CD45RBhi and CD45RBlo populations. Relative to CD45RBlo...

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Main Authors: Scott M. Krummey, Anna B. Morris, Jesica R. Jacobs, Donald J. McGuire, Satomi Ando, Katherine P. Tong, Weiwen Zhang, Jennifer Robertson, Sara A. Guasch, Koichi Araki, Christian P. Larsen, Brian D. Evavold, Haydn T. Kissick, Mandy L. Ford
Format: Article
Language:English
Published: Elsevier 2020-02-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124720300255
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author Scott M. Krummey
Anna B. Morris
Jesica R. Jacobs
Donald J. McGuire
Satomi Ando
Katherine P. Tong
Weiwen Zhang
Jennifer Robertson
Sara A. Guasch
Koichi Araki
Christian P. Larsen
Brian D. Evavold
Haydn T. Kissick
Mandy L. Ford
author_facet Scott M. Krummey
Anna B. Morris
Jesica R. Jacobs
Donald J. McGuire
Satomi Ando
Katherine P. Tong
Weiwen Zhang
Jennifer Robertson
Sara A. Guasch
Koichi Araki
Christian P. Larsen
Brian D. Evavold
Haydn T. Kissick
Mandy L. Ford
author_sort Scott M. Krummey
collection DOAJ
description Summary: The identity of CD45 isoforms on the T cell surface changes following the activation of naive T cells and impacts intracellular signaling. In this study, we find that the anti-viral memory CD8+ T pool is unexpectedly comprised of both CD45RBhi and CD45RBlo populations. Relative to CD45RBlo memory T cells, CD45RBhi memory T cells have lower affinity and display greater clonal diversity, as well as a persistent CD27hi phenotype. The CD45RBhi memory population displays a homeostatic survival advantage in vivo relative to CD45RBlo memory, and long-lived high-affinity cells that persisted long term convert from CD45RBlo to CD45RBhi. Human CD45RO+ memory is comprised of both CD45RBhi and CD45RBlo populations with distinct phenotypes, and antigen-specific memory to two viruses is predominantly CD45RBhi. These data demonstrate that CD45RB status is distinct from the conventional central/effector T cell memory classification and has potential utility for monitoring and characterizing pathogen-specific CD8+ T cell responses. : Krummey et al. show that viral CD8+ T cell memory has heterogeneous CD45 isoform expression. Low-affinity CD8+ T cells have high CD45RB expression and a CD27hiCD62Lhi phenotype relative to high-affinity CD45RBlo CD8+ T cells, which possess an effector-like phenotype. CD45RBhi cells survive better under homeostatic conditions in vivo. Keywords: T cell memory, TCR affinity, CD45
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spelling doaj.art-d69652ad5ff041889716115077fdfc7b2022-12-21T18:22:41ZengElsevierCell Reports2211-12472020-02-0130512821291.e5CD45RB Status of CD8+ T Cell Memory Defines T Cell Receptor Affinity and PersistenceScott M. Krummey0Anna B. Morris1Jesica R. Jacobs2Donald J. McGuire3Satomi Ando4Katherine P. Tong5Weiwen Zhang6Jennifer Robertson7Sara A. Guasch8Koichi Araki9Christian P. Larsen10Brian D. Evavold11Haydn T. Kissick12Mandy L. Ford13Emory Transplant Center, Emory University School of Medicine, Atlanta, GA, USA; Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA; Corresponding authorEmory Transplant Center, Emory University School of Medicine, Atlanta, GA, USADepartment of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USADepartment of Microbiology & Immunology, Emory University School of Medicine, Atlanta, GA, USADepartment of Microbiology & Immunology, Emory University School of Medicine, Atlanta, GA, USAEmory Transplant Center, Emory University School of Medicine, Atlanta, GA, USAEmory Transplant Center, Emory University School of Medicine, Atlanta, GA, USAEmory Transplant Center, Emory University School of Medicine, Atlanta, GA, USAEmory Transplant Center, Emory University School of Medicine, Atlanta, GA, USADepartment of Microbiology & Immunology, Emory University School of Medicine, Atlanta, GA, USAEmory Transplant Center, Emory University School of Medicine, Atlanta, GA, USADepartment of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USADepartment of Urology, Emory University School of Medicine, Atlanta, GA, USAEmory Transplant Center, Emory University School of Medicine, Atlanta, GA, USASummary: The identity of CD45 isoforms on the T cell surface changes following the activation of naive T cells and impacts intracellular signaling. In this study, we find that the anti-viral memory CD8+ T pool is unexpectedly comprised of both CD45RBhi and CD45RBlo populations. Relative to CD45RBlo memory T cells, CD45RBhi memory T cells have lower affinity and display greater clonal diversity, as well as a persistent CD27hi phenotype. The CD45RBhi memory population displays a homeostatic survival advantage in vivo relative to CD45RBlo memory, and long-lived high-affinity cells that persisted long term convert from CD45RBlo to CD45RBhi. Human CD45RO+ memory is comprised of both CD45RBhi and CD45RBlo populations with distinct phenotypes, and antigen-specific memory to two viruses is predominantly CD45RBhi. These data demonstrate that CD45RB status is distinct from the conventional central/effector T cell memory classification and has potential utility for monitoring and characterizing pathogen-specific CD8+ T cell responses. : Krummey et al. show that viral CD8+ T cell memory has heterogeneous CD45 isoform expression. Low-affinity CD8+ T cells have high CD45RB expression and a CD27hiCD62Lhi phenotype relative to high-affinity CD45RBlo CD8+ T cells, which possess an effector-like phenotype. CD45RBhi cells survive better under homeostatic conditions in vivo. Keywords: T cell memory, TCR affinity, CD45http://www.sciencedirect.com/science/article/pii/S2211124720300255
spellingShingle Scott M. Krummey
Anna B. Morris
Jesica R. Jacobs
Donald J. McGuire
Satomi Ando
Katherine P. Tong
Weiwen Zhang
Jennifer Robertson
Sara A. Guasch
Koichi Araki
Christian P. Larsen
Brian D. Evavold
Haydn T. Kissick
Mandy L. Ford
CD45RB Status of CD8+ T Cell Memory Defines T Cell Receptor Affinity and Persistence
Cell Reports
title CD45RB Status of CD8+ T Cell Memory Defines T Cell Receptor Affinity and Persistence
title_full CD45RB Status of CD8+ T Cell Memory Defines T Cell Receptor Affinity and Persistence
title_fullStr CD45RB Status of CD8+ T Cell Memory Defines T Cell Receptor Affinity and Persistence
title_full_unstemmed CD45RB Status of CD8+ T Cell Memory Defines T Cell Receptor Affinity and Persistence
title_short CD45RB Status of CD8+ T Cell Memory Defines T Cell Receptor Affinity and Persistence
title_sort cd45rb status of cd8 t cell memory defines t cell receptor affinity and persistence
url http://www.sciencedirect.com/science/article/pii/S2211124720300255
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