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Differential targeting of viral components by CD4+ versus CD8+ T lymphocytes in dengue virus infection

Research output: Contribution to journalArticle

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Differential targeting of viral components by CD4+ versus CD8+ T lymphocytes in dengue virus infection. / Rivino, Laura; Kumaran, Emmanuelle A P; Jovanovic, Vojislav; Nadua, Karen; Teo, En Wei; Pang, Shyue Wei; Teo, Guo Hui; Gan, Victor Chih Hao; Lye, David C; Leo, Yee Sin; Hanson, Brendon J; Smith, Kenneth G C; Bertoletti, Antonio; Kemeny, David M; MacAry, Paul A.

In: Journal of Virology, Vol. 87, No. 5, 03.2013, p. 2693-706.

Research output: Contribution to journalArticle

Harvard

Rivino, L, Kumaran, EAP, Jovanovic, V, Nadua, K, Teo, EW, Pang, SW, Teo, GH, Gan, VCH, Lye, DC, Leo, YS, Hanson, BJ, Smith, KGC, Bertoletti, A, Kemeny, DM & MacAry, PA 2013, 'Differential targeting of viral components by CD4+ versus CD8+ T lymphocytes in dengue virus infection', Journal of Virology, vol. 87, no. 5, pp. 2693-706. https://doi.org/10.1128/JVI.02675-12

APA

Rivino, L., Kumaran, E. A. P., Jovanovic, V., Nadua, K., Teo, E. W., Pang, S. W., ... MacAry, P. A. (2013). Differential targeting of viral components by CD4+ versus CD8+ T lymphocytes in dengue virus infection. Journal of Virology, 87(5), 2693-706. https://doi.org/10.1128/JVI.02675-12

Vancouver

Rivino L, Kumaran EAP, Jovanovic V, Nadua K, Teo EW, Pang SW et al. Differential targeting of viral components by CD4+ versus CD8+ T lymphocytes in dengue virus infection. Journal of Virology. 2013 Mar;87(5):2693-706. https://doi.org/10.1128/JVI.02675-12

Author

Rivino, Laura ; Kumaran, Emmanuelle A P ; Jovanovic, Vojislav ; Nadua, Karen ; Teo, En Wei ; Pang, Shyue Wei ; Teo, Guo Hui ; Gan, Victor Chih Hao ; Lye, David C ; Leo, Yee Sin ; Hanson, Brendon J ; Smith, Kenneth G C ; Bertoletti, Antonio ; Kemeny, David M ; MacAry, Paul A. / Differential targeting of viral components by CD4+ versus CD8+ T lymphocytes in dengue virus infection. In: Journal of Virology. 2013 ; Vol. 87, No. 5. pp. 2693-706.

Bibtex

@article{5fde84417e22421592516244b7d9a244,
title = "Differential targeting of viral components by CD4+ versus CD8+ T lymphocytes in dengue virus infection",
abstract = "Dengue virus (DENV) is the principal arthropod-borne viral pathogen afflicting human populations. While repertoires of antibodies to DENV have been linked to protection or enhanced infection, the role of T lymphocytes in these processes remains poorly defined. This study provides a comprehensive overview of CD4(+) and CD8(+) T cell epitope reactivities against the DENV 2 proteome in adult patients experiencing secondary DENV infection. Dengue virus-specific T cell responses directed against an overlapping 15mer peptide library spanning the DENV 2 proteome were analyzed ex vivo by enzyme-linked immunosorbent spot assay, and recognition of individual peptides was further characterized in specific T cell lines. Thirty novel T cell epitopes were identified, 9 of which are CD4(+) and 21 are CD8(+) T cell epitopes. We observe that whereas CD8(+) T cell epitopes preferentially target nonstructural proteins (NS3 and NS5), CD4(+) epitopes are skewed toward recognition of viral components that are also targeted by B lymphocytes (envelope, capsid, and NS1). Consistently, a large proportion of dengue virus-specific CD4(+) T cells have phenotypic characteristics of circulating follicular helper T cells (CXCR5 expression and production of interleukin-21 or gamma interferon), suggesting that they are interacting with B cells in vivo. This study shows that during a dengue virus infection, the protein targets of human CD4(+) and CD8(+) T cells are largely distinct, thus highlighting key differences in the immunodominance of DENV proteins for these two cell types. This has important implications for our understanding of how the two arms of the human adaptive immune system are differentially targeted and employed as part of our response to DENV infection.",
keywords = "Adult, B-Lymphocytes/immunology, CD4-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/immunology, Capsid Proteins/immunology, Cells, Cultured, Dengue/immunology, Dengue Virus/immunology, Epitopes, T-Lymphocyte/immunology, Female, Humans, Interferon-gamma/biosynthesis, Interleukins/biosynthesis, Male, Middle Aged, Proteome/immunology, RNA Helicases/immunology, Receptors, CXCR5/biosynthesis, Serine Endopeptidases/immunology, Viral Envelope Proteins/immunology, Viral Nonstructural Proteins/immunology",
author = "Laura Rivino and Kumaran, {Emmanuelle A P} and Vojislav Jovanovic and Karen Nadua and Teo, {En Wei} and Pang, {Shyue Wei} and Teo, {Guo Hui} and Gan, {Victor Chih Hao} and Lye, {David C} and Leo, {Yee Sin} and Hanson, {Brendon J} and Smith, {Kenneth G C} and Antonio Bertoletti and Kemeny, {David M} and MacAry, {Paul A}",
year = "2013",
month = "3",
doi = "10.1128/JVI.02675-12",
language = "English",
volume = "87",
pages = "2693--706",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "5",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - Differential targeting of viral components by CD4+ versus CD8+ T lymphocytes in dengue virus infection

AU - Rivino, Laura

AU - Kumaran, Emmanuelle A P

AU - Jovanovic, Vojislav

AU - Nadua, Karen

AU - Teo, En Wei

AU - Pang, Shyue Wei

AU - Teo, Guo Hui

AU - Gan, Victor Chih Hao

AU - Lye, David C

AU - Leo, Yee Sin

AU - Hanson, Brendon J

AU - Smith, Kenneth G C

AU - Bertoletti, Antonio

AU - Kemeny, David M

AU - MacAry, Paul A

PY - 2013/3

Y1 - 2013/3

N2 - Dengue virus (DENV) is the principal arthropod-borne viral pathogen afflicting human populations. While repertoires of antibodies to DENV have been linked to protection or enhanced infection, the role of T lymphocytes in these processes remains poorly defined. This study provides a comprehensive overview of CD4(+) and CD8(+) T cell epitope reactivities against the DENV 2 proteome in adult patients experiencing secondary DENV infection. Dengue virus-specific T cell responses directed against an overlapping 15mer peptide library spanning the DENV 2 proteome were analyzed ex vivo by enzyme-linked immunosorbent spot assay, and recognition of individual peptides was further characterized in specific T cell lines. Thirty novel T cell epitopes were identified, 9 of which are CD4(+) and 21 are CD8(+) T cell epitopes. We observe that whereas CD8(+) T cell epitopes preferentially target nonstructural proteins (NS3 and NS5), CD4(+) epitopes are skewed toward recognition of viral components that are also targeted by B lymphocytes (envelope, capsid, and NS1). Consistently, a large proportion of dengue virus-specific CD4(+) T cells have phenotypic characteristics of circulating follicular helper T cells (CXCR5 expression and production of interleukin-21 or gamma interferon), suggesting that they are interacting with B cells in vivo. This study shows that during a dengue virus infection, the protein targets of human CD4(+) and CD8(+) T cells are largely distinct, thus highlighting key differences in the immunodominance of DENV proteins for these two cell types. This has important implications for our understanding of how the two arms of the human adaptive immune system are differentially targeted and employed as part of our response to DENV infection.

AB - Dengue virus (DENV) is the principal arthropod-borne viral pathogen afflicting human populations. While repertoires of antibodies to DENV have been linked to protection or enhanced infection, the role of T lymphocytes in these processes remains poorly defined. This study provides a comprehensive overview of CD4(+) and CD8(+) T cell epitope reactivities against the DENV 2 proteome in adult patients experiencing secondary DENV infection. Dengue virus-specific T cell responses directed against an overlapping 15mer peptide library spanning the DENV 2 proteome were analyzed ex vivo by enzyme-linked immunosorbent spot assay, and recognition of individual peptides was further characterized in specific T cell lines. Thirty novel T cell epitopes were identified, 9 of which are CD4(+) and 21 are CD8(+) T cell epitopes. We observe that whereas CD8(+) T cell epitopes preferentially target nonstructural proteins (NS3 and NS5), CD4(+) epitopes are skewed toward recognition of viral components that are also targeted by B lymphocytes (envelope, capsid, and NS1). Consistently, a large proportion of dengue virus-specific CD4(+) T cells have phenotypic characteristics of circulating follicular helper T cells (CXCR5 expression and production of interleukin-21 or gamma interferon), suggesting that they are interacting with B cells in vivo. This study shows that during a dengue virus infection, the protein targets of human CD4(+) and CD8(+) T cells are largely distinct, thus highlighting key differences in the immunodominance of DENV proteins for these two cell types. This has important implications for our understanding of how the two arms of the human adaptive immune system are differentially targeted and employed as part of our response to DENV infection.

KW - Adult

KW - B-Lymphocytes/immunology

KW - CD4-Positive T-Lymphocytes/immunology

KW - CD8-Positive T-Lymphocytes/immunology

KW - Capsid Proteins/immunology

KW - Cells, Cultured

KW - Dengue/immunology

KW - Dengue Virus/immunology

KW - Epitopes, T-Lymphocyte/immunology

KW - Female

KW - Humans

KW - Interferon-gamma/biosynthesis

KW - Interleukins/biosynthesis

KW - Male

KW - Middle Aged

KW - Proteome/immunology

KW - RNA Helicases/immunology

KW - Receptors, CXCR5/biosynthesis

KW - Serine Endopeptidases/immunology

KW - Viral Envelope Proteins/immunology

KW - Viral Nonstructural Proteins/immunology

U2 - 10.1128/JVI.02675-12

DO - 10.1128/JVI.02675-12

M3 - Article

C2 - 23255803

VL - 87

SP - 2693

EP - 2706

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 5

ER -