Publication

Lymphocryptovirus Infection of Nonhuman Primate B Cells Converts Destructive into Productive Processing of the Pathogenic CD8 T Cell Epitope in Myelin Oligodendrocyte Glycoprotein

Jagessar, S. A., Holtman, I. R., Hofman, S., Morandi, E., Heijmans, N., Laman, J. D., Gran, B., Faber, B. W., van Kasteren, S. I., Eggen, B. J. L. & 't Hart, B. A., 15-Aug-2016, In : Journal of Immunology. 197, 4, p. 1074-1088 15 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Jagessar, S. A., Holtman, I. R., Hofman, S., Morandi, E., Heijmans, N., Laman, J. D., Gran, B., Faber, B. W., van Kasteren, S. I., Eggen, B. J. L., & 't Hart, B. A. (2016). Lymphocryptovirus Infection of Nonhuman Primate B Cells Converts Destructive into Productive Processing of the Pathogenic CD8 T Cell Epitope in Myelin Oligodendrocyte Glycoprotein. Journal of Immunology, 197(4), 1074-1088. https://doi.org/10.4049/jimmunol.1600124

Author

Jagessar, S. Anwar ; Holtman, Inge R. ; Hofman, Sam ; Morandi, Elena ; Heijmans, Nicole ; Laman, Jon D. ; Gran, Bruno ; Faber, Bart W. ; van Kasteren, Sander I. ; Eggen, Bart J. L. ; 't Hart, Bert A. / Lymphocryptovirus Infection of Nonhuman Primate B Cells Converts Destructive into Productive Processing of the Pathogenic CD8 T Cell Epitope in Myelin Oligodendrocyte Glycoprotein. In: Journal of Immunology. 2016 ; Vol. 197, No. 4. pp. 1074-1088.

Harvard

Jagessar, SA, Holtman, IR, Hofman, S, Morandi, E, Heijmans, N, Laman, JD, Gran, B, Faber, BW, van Kasteren, SI, Eggen, BJL & 't Hart, BA 2016, 'Lymphocryptovirus Infection of Nonhuman Primate B Cells Converts Destructive into Productive Processing of the Pathogenic CD8 T Cell Epitope in Myelin Oligodendrocyte Glycoprotein', Journal of Immunology, vol. 197, no. 4, pp. 1074-1088. https://doi.org/10.4049/jimmunol.1600124

Standard

Lymphocryptovirus Infection of Nonhuman Primate B Cells Converts Destructive into Productive Processing of the Pathogenic CD8 T Cell Epitope in Myelin Oligodendrocyte Glycoprotein. / Jagessar, S. Anwar; Holtman, Inge R.; Hofman, Sam; Morandi, Elena; Heijmans, Nicole; Laman, Jon D.; Gran, Bruno; Faber, Bart W.; van Kasteren, Sander I.; Eggen, Bart J. L.; 't Hart, Bert A.

In: Journal of Immunology, Vol. 197, No. 4, 15.08.2016, p. 1074-1088.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Jagessar SA, Holtman IR, Hofman S, Morandi E, Heijmans N, Laman JD et al. Lymphocryptovirus Infection of Nonhuman Primate B Cells Converts Destructive into Productive Processing of the Pathogenic CD8 T Cell Epitope in Myelin Oligodendrocyte Glycoprotein. Journal of Immunology. 2016 Aug 15;197(4):1074-1088. https://doi.org/10.4049/jimmunol.1600124


BibTeX

@article{bbebb02668974761ba07d761b41de0b1,
title = "Lymphocryptovirus Infection of Nonhuman Primate B Cells Converts Destructive into Productive Processing of the Pathogenic CD8 T Cell Epitope in Myelin Oligodendrocyte Glycoprotein",
abstract = "EBV is the major infectious environmental risk factor for multiple sclerosis (MS), but the underlying mechanisms remain obscure. Patient studies do not allow manipulation in vivo. We used the experimental autoimmune encephalomyelitis (EAE) models in the common marmoset and rhesus monkey to model the association of EBV and MS. We report that B cells infected with EBV-related lymphocryptovirus (LCV) are requisite APCs for MHC-E-restricted autoaggressive effector memory CTLs specific for the immunodominant epitope 40-48 of myelin oligodendrocyte glycoprotein (MOG). These T cells drive the EAE pathogenesis to irreversible neurologic deficit. The aim of this study was to determine why LCV infection is important for this pathogenic role of B cells. Transcriptome comparison of LCV-infected B cells and CD20(+) spleen cells from rhesus monkeys shows increased expression of genes encoding elements of the Ag cross-presentation machinery (i.e., of proteasome maturation protein and immunoproteasome subunits) and enhanced expression of MHC-E and of costimulatory molecules (CD70 and CD80, but not CD86). It was also shown that altered expression of endolysosomal proteases (cathepsins) mitigates the fast endolysosomal degradation of the MOG40-48 core epitope. Finally, LCV infection also induced expression of LC3-II+ cytosolic structures resembling autophagosomes, which seem to form an intracellular compartment where the MOG40-48 epitope is protected against proteolytic degradation by the endolysosomal serine protease cathepsin G. In conclusion, LCV infection induces a variety of changes in B cells that underlies the conversion of destructive processing of the immunodominant MOG40-48 epitope into productive processing and cross-presentation to strongly autoaggressive CTLs.",
keywords = "EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS, MULTIPLE-SCLEROSIS, CROSS-PRESENTATION, MARMOSET MONKEYS, DENDRITIC CELLS, CATHEPSIN-G, PROTEASE INHIBITOR, COMMON MARMOSETS, EAE MODEL, IN-VIVO",
author = "Jagessar, {S. Anwar} and Holtman, {Inge R.} and Sam Hofman and Elena Morandi and Nicole Heijmans and Laman, {Jon D.} and Bruno Gran and Faber, {Bart W.} and {van Kasteren}, {Sander I.} and Eggen, {Bart J. L.} and {'t Hart}, {Bert A.}",
note = "Copyright {\textcopyright} 2016 by The American Association of Immunologists, Inc.",
year = "2016",
month = aug,
day = "15",
doi = "10.4049/jimmunol.1600124",
language = "English",
volume = "197",
pages = "1074--1088",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "AMER ASSOC IMMUNOLOGISTS",
number = "4",

}

RIS

TY - JOUR

T1 - Lymphocryptovirus Infection of Nonhuman Primate B Cells Converts Destructive into Productive Processing of the Pathogenic CD8 T Cell Epitope in Myelin Oligodendrocyte Glycoprotein

AU - Jagessar, S. Anwar

AU - Holtman, Inge R.

AU - Hofman, Sam

AU - Morandi, Elena

AU - Heijmans, Nicole

AU - Laman, Jon D.

AU - Gran, Bruno

AU - Faber, Bart W.

AU - van Kasteren, Sander I.

AU - Eggen, Bart J. L.

AU - 't Hart, Bert A.

N1 - Copyright © 2016 by The American Association of Immunologists, Inc.

PY - 2016/8/15

Y1 - 2016/8/15

N2 - EBV is the major infectious environmental risk factor for multiple sclerosis (MS), but the underlying mechanisms remain obscure. Patient studies do not allow manipulation in vivo. We used the experimental autoimmune encephalomyelitis (EAE) models in the common marmoset and rhesus monkey to model the association of EBV and MS. We report that B cells infected with EBV-related lymphocryptovirus (LCV) are requisite APCs for MHC-E-restricted autoaggressive effector memory CTLs specific for the immunodominant epitope 40-48 of myelin oligodendrocyte glycoprotein (MOG). These T cells drive the EAE pathogenesis to irreversible neurologic deficit. The aim of this study was to determine why LCV infection is important for this pathogenic role of B cells. Transcriptome comparison of LCV-infected B cells and CD20(+) spleen cells from rhesus monkeys shows increased expression of genes encoding elements of the Ag cross-presentation machinery (i.e., of proteasome maturation protein and immunoproteasome subunits) and enhanced expression of MHC-E and of costimulatory molecules (CD70 and CD80, but not CD86). It was also shown that altered expression of endolysosomal proteases (cathepsins) mitigates the fast endolysosomal degradation of the MOG40-48 core epitope. Finally, LCV infection also induced expression of LC3-II+ cytosolic structures resembling autophagosomes, which seem to form an intracellular compartment where the MOG40-48 epitope is protected against proteolytic degradation by the endolysosomal serine protease cathepsin G. In conclusion, LCV infection induces a variety of changes in B cells that underlies the conversion of destructive processing of the immunodominant MOG40-48 epitope into productive processing and cross-presentation to strongly autoaggressive CTLs.

AB - EBV is the major infectious environmental risk factor for multiple sclerosis (MS), but the underlying mechanisms remain obscure. Patient studies do not allow manipulation in vivo. We used the experimental autoimmune encephalomyelitis (EAE) models in the common marmoset and rhesus monkey to model the association of EBV and MS. We report that B cells infected with EBV-related lymphocryptovirus (LCV) are requisite APCs for MHC-E-restricted autoaggressive effector memory CTLs specific for the immunodominant epitope 40-48 of myelin oligodendrocyte glycoprotein (MOG). These T cells drive the EAE pathogenesis to irreversible neurologic deficit. The aim of this study was to determine why LCV infection is important for this pathogenic role of B cells. Transcriptome comparison of LCV-infected B cells and CD20(+) spleen cells from rhesus monkeys shows increased expression of genes encoding elements of the Ag cross-presentation machinery (i.e., of proteasome maturation protein and immunoproteasome subunits) and enhanced expression of MHC-E and of costimulatory molecules (CD70 and CD80, but not CD86). It was also shown that altered expression of endolysosomal proteases (cathepsins) mitigates the fast endolysosomal degradation of the MOG40-48 core epitope. Finally, LCV infection also induced expression of LC3-II+ cytosolic structures resembling autophagosomes, which seem to form an intracellular compartment where the MOG40-48 epitope is protected against proteolytic degradation by the endolysosomal serine protease cathepsin G. In conclusion, LCV infection induces a variety of changes in B cells that underlies the conversion of destructive processing of the immunodominant MOG40-48 epitope into productive processing and cross-presentation to strongly autoaggressive CTLs.

KW - EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

KW - MULTIPLE-SCLEROSIS

KW - CROSS-PRESENTATION

KW - MARMOSET MONKEYS

KW - DENDRITIC CELLS

KW - CATHEPSIN-G

KW - PROTEASE INHIBITOR

KW - COMMON MARMOSETS

KW - EAE MODEL

KW - IN-VIVO

U2 - 10.4049/jimmunol.1600124

DO - 10.4049/jimmunol.1600124

M3 - Article

C2 - 27412414

VL - 197

SP - 1074

EP - 1088

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 4

ER -

ID: 33885489