CD8+ T cells from mice transnuclear for a TCR that recognizes a single H-2Kb-restricted MHV68 epitope derived from gB-ORF8 help control infection

Sharvan Sehrawat; Oktay Kirak; Paul Albert Koenig; Marisa K. Isaacson; Sofia Marques; Gunes Bozkurt; J. Pedro Simas; Rudolph Jaenisch; Hidde L. Ploegh

doi:10.1016/j.celrep.2012.03.009

CD8+ T cells from mice transnuclear for a TCR that recognizes a single H-2Kb-restricted MHV68 epitope derived from gB-ORF8 help control infection

Sharvan Sehrawat
, Oktay Kirak
, Paul Albert Koenig
, Marisa K. Isaacson
, Sofia Marques
, Gunes Bozkurt
, J. Pedro Simas
, Rudolph Jaenisch
, Hidde L. Ploegh^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

Abstract

To study the CD8+ T cell response against a mouse γ-herpes virus, we generated Kb-MHV-68-ORF8604-612RAG-/- CD8+ T cell receptor transnuclear (TN) mice as a source of virus-specific CD8+ T cells. Kb-ORF8-Tet+ CD8+ T cells, expanded in the course of a resolving MHV-68 infection, served as a source of nucleus donors. Various in vivo and ex vivo assay criteria demonstrated the fine specificity and functionality of TN cells. TN cells proliferated extensively in response to viral infection, helped control viral burden, and exhibited a phenotype similar to that of endogenous Kb-ORF8-Tet+ cells. When compared to OT-1 cells, TN cells displayed distinct properties in response to lymphopenia and cognate antigen stimulation, which may be attributable to the affinity of the TCR expressed by the TN cells. The availability of MHV-68-specific CD8+ TCR TN mice provides a new tool for investigating aspects of host-pathogen interactions unique to γ-herpes viruses.

Original language	English
Pages (from-to)	461-471
Number of pages	11
Journal	Cell reports
Volume	1
Issue number	5
DOIs	https://doi.org/10.1016/j.celrep.2012.03.009
Publication status	Published - 31 May 2012
Externally published	Yes

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10.1016/j.celrep.2012.03.009Licence: CC BY-NC-ND

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@article{90efb5a6897045c080aa930e2efa3d0c,

title = "CD8+ T cells from mice transnuclear for a TCR that recognizes a single H-2Kb-restricted MHV68 epitope derived from gB-ORF8 help control infection",

abstract = "To study the CD8+ T cell response against a mouse γ-herpes virus, we generated Kb-MHV-68-ORF8604-612RAG-/- CD8+ T cell receptor transnuclear (TN) mice as a source of virus-specific CD8+ T cells. Kb-ORF8-Tet+ CD8+ T cells, expanded in the course of a resolving MHV-68 infection, served as a source of nucleus donors. Various in vivo and ex vivo assay criteria demonstrated the fine specificity and functionality of TN cells. TN cells proliferated extensively in response to viral infection, helped control viral burden, and exhibited a phenotype similar to that of endogenous Kb-ORF8-Tet+ cells. When compared to OT-1 cells, TN cells displayed distinct properties in response to lymphopenia and cognate antigen stimulation, which may be attributable to the affinity of the TCR expressed by the TN cells. The availability of MHV-68-specific CD8+ TCR TN mice provides a new tool for investigating aspects of host-pathogen interactions unique to γ-herpes viruses.",

author = "Sharvan Sehrawat and Oktay Kirak and Koenig, \{Paul Albert\} and Isaacson, \{Marisa K.\} and Sofia Marques and Gunes Bozkurt and Simas, \{J. Pedro\} and Rudolph Jaenisch and Ploegh, \{Hidde L.\}",

note = "Funding Information: We thank Barry T. Rouse of the University of Tennessee for critically reading the manuscript. We acknowledge technical help provided by Patti Wisniewski with FACS and Tom DiCesare for helping with figure drawing. The work was supported by funding from NIH. ",

year = "2012",

month = may,

day = "31",

doi = "10.1016/j.celrep.2012.03.009",

language = "English",

volume = "1",

pages = "461--471",

journal = "Cell reports",

issn = "2211-1247",

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TY - JOUR

T1 - CD8+ T cells from mice transnuclear for a TCR that recognizes a single H-2Kb-restricted MHV68 epitope derived from gB-ORF8 help control infection

AU - Sehrawat, Sharvan

AU - Kirak, Oktay

AU - Koenig, Paul Albert

AU - Isaacson, Marisa K.

AU - Marques, Sofia

AU - Bozkurt, Gunes

AU - Simas, J. Pedro

AU - Jaenisch, Rudolph

AU - Ploegh, Hidde L.

N1 - Funding Information: We thank Barry T. Rouse of the University of Tennessee for critically reading the manuscript. We acknowledge technical help provided by Patti Wisniewski with FACS and Tom DiCesare for helping with figure drawing. The work was supported by funding from NIH.

PY - 2012/5/31

Y1 - 2012/5/31

N2 - To study the CD8+ T cell response against a mouse γ-herpes virus, we generated Kb-MHV-68-ORF8604-612RAG-/- CD8+ T cell receptor transnuclear (TN) mice as a source of virus-specific CD8+ T cells. Kb-ORF8-Tet+ CD8+ T cells, expanded in the course of a resolving MHV-68 infection, served as a source of nucleus donors. Various in vivo and ex vivo assay criteria demonstrated the fine specificity and functionality of TN cells. TN cells proliferated extensively in response to viral infection, helped control viral burden, and exhibited a phenotype similar to that of endogenous Kb-ORF8-Tet+ cells. When compared to OT-1 cells, TN cells displayed distinct properties in response to lymphopenia and cognate antigen stimulation, which may be attributable to the affinity of the TCR expressed by the TN cells. The availability of MHV-68-specific CD8+ TCR TN mice provides a new tool for investigating aspects of host-pathogen interactions unique to γ-herpes viruses.

AB - To study the CD8+ T cell response against a mouse γ-herpes virus, we generated Kb-MHV-68-ORF8604-612RAG-/- CD8+ T cell receptor transnuclear (TN) mice as a source of virus-specific CD8+ T cells. Kb-ORF8-Tet+ CD8+ T cells, expanded in the course of a resolving MHV-68 infection, served as a source of nucleus donors. Various in vivo and ex vivo assay criteria demonstrated the fine specificity and functionality of TN cells. TN cells proliferated extensively in response to viral infection, helped control viral burden, and exhibited a phenotype similar to that of endogenous Kb-ORF8-Tet+ cells. When compared to OT-1 cells, TN cells displayed distinct properties in response to lymphopenia and cognate antigen stimulation, which may be attributable to the affinity of the TCR expressed by the TN cells. The availability of MHV-68-specific CD8+ TCR TN mice provides a new tool for investigating aspects of host-pathogen interactions unique to γ-herpes viruses.

UR - https://www.scopus.com/pages/publications/84861695392

U2 - 10.1016/j.celrep.2012.03.009

DO - 10.1016/j.celrep.2012.03.009

M3 - Article

C2 - 22832272

AN - SCOPUS:84861695392

SN - 2211-1247

VL - 1

SP - 461

EP - 471

JO - Cell reports

JF - Cell reports

IS - 5

ER -

CD8+ T cells from mice transnuclear for a TCR that recognizes a single H-2Kb-restricted MHV68 epitope derived from gB-ORF8 help control infection

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