Institut for Biomedicin

Thomas Vorup-Jensen

In silico and in vivo analysis of Toxoplasma gondii epitopes by correlating survival data with peptide-MHC-I binding affinities

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In silico and in vivo analysis of Toxoplasma gondii epitopes by correlating survival data with peptide-MHC-I binding affinities. / Huang, Si-Yang; Jensen, Maria Risager; Rosenberg, Carina Agerbo; Zhu, Xing-Quan; Petersen, Eskild; Vorup-Jensen, Thomas.

I: International Journal of Infectious Diseases, Bind 48, 22.04.2016, s. 14-19.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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Huang, Si-Yang ; Jensen, Maria Risager ; Rosenberg, Carina Agerbo ; Zhu, Xing-Quan ; Petersen, Eskild ; Vorup-Jensen, Thomas. / In silico and in vivo analysis of Toxoplasma gondii epitopes by correlating survival data with peptide-MHC-I binding affinities. I: International Journal of Infectious Diseases. 2016 ; Bind 48. s. 14-19.

Bibtex

@article{e095c65910ae4d37860067df712bca18,
title = "In silico and in vivo analysis of Toxoplasma gondii epitopes by correlating survival data with peptide-MHC-I binding affinities",
abstract = "BACKGROUND: Protein antigens comprising peptide motifs with high binding affinity to major histocompatibility complex class I (MHC-I) molecules are expected to induce a stronger cytotoxic T-lymphocyte response and thus provide better protection against infection with microorganisms where cytotoxic T-cells are the main effector arm of the immune system.METHODS: Data on cyst formation and survival were extracted from past studies on the DNA immunization of mice with plasmids coding for Toxoplasma gondii antigens. From in silico analyses of the vaccine antigens, the correlation was tested between the predicted affinity for MHC-I molecules of the vaccine peptides and the survival of immunized mice after challenge with T. gondii. ELISPOT analysis was used for the experimental testing of peptide immunogenicity.RESULTS: Predictions for the Db MHC-I molecule produced a strong, negative correlation between survival and the dissociation constant of vaccine-derived peptides. The in silico analyses of nine T. gondii antigens identified peptides with a predicted dissociation constant in the interval from 10nM to 40μM. ELISPOT assays with splenocytes from T. gondii-infected mice further supported the importance of the peptide affinity for MHC-I.CONCLUSIONS: In silico analysis clearly helped the search for protective vaccine antigens. The ELISPOT analysis confirmed that the predicted T-cell epitopes were immunogenic by their ability to release interferon gamma in spleen cells.",
author = "Si-Yang Huang and Jensen, {Maria Risager} and Rosenberg, {Carina Agerbo} and Xing-Quan Zhu and Eskild Petersen and Thomas Vorup-Jensen",
note = "Copyright {\circledC} 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.",
year = "2016",
month = "4",
day = "22",
doi = "10.1016/j.ijid.2016.04.014",
language = "English",
volume = "48",
pages = "14--19",
journal = "International Journal of Infectious Diseases",
issn = "1201-9712",
publisher = "Elsevier Ltd",

}

RIS

TY - JOUR

T1 - In silico and in vivo analysis of Toxoplasma gondii epitopes by correlating survival data with peptide-MHC-I binding affinities

AU - Huang, Si-Yang

AU - Jensen, Maria Risager

AU - Rosenberg, Carina Agerbo

AU - Zhu, Xing-Quan

AU - Petersen, Eskild

AU - Vorup-Jensen, Thomas

N1 - Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

PY - 2016/4/22

Y1 - 2016/4/22

N2 - BACKGROUND: Protein antigens comprising peptide motifs with high binding affinity to major histocompatibility complex class I (MHC-I) molecules are expected to induce a stronger cytotoxic T-lymphocyte response and thus provide better protection against infection with microorganisms where cytotoxic T-cells are the main effector arm of the immune system.METHODS: Data on cyst formation and survival were extracted from past studies on the DNA immunization of mice with plasmids coding for Toxoplasma gondii antigens. From in silico analyses of the vaccine antigens, the correlation was tested between the predicted affinity for MHC-I molecules of the vaccine peptides and the survival of immunized mice after challenge with T. gondii. ELISPOT analysis was used for the experimental testing of peptide immunogenicity.RESULTS: Predictions for the Db MHC-I molecule produced a strong, negative correlation between survival and the dissociation constant of vaccine-derived peptides. The in silico analyses of nine T. gondii antigens identified peptides with a predicted dissociation constant in the interval from 10nM to 40μM. ELISPOT assays with splenocytes from T. gondii-infected mice further supported the importance of the peptide affinity for MHC-I.CONCLUSIONS: In silico analysis clearly helped the search for protective vaccine antigens. The ELISPOT analysis confirmed that the predicted T-cell epitopes were immunogenic by their ability to release interferon gamma in spleen cells.

AB - BACKGROUND: Protein antigens comprising peptide motifs with high binding affinity to major histocompatibility complex class I (MHC-I) molecules are expected to induce a stronger cytotoxic T-lymphocyte response and thus provide better protection against infection with microorganisms where cytotoxic T-cells are the main effector arm of the immune system.METHODS: Data on cyst formation and survival were extracted from past studies on the DNA immunization of mice with plasmids coding for Toxoplasma gondii antigens. From in silico analyses of the vaccine antigens, the correlation was tested between the predicted affinity for MHC-I molecules of the vaccine peptides and the survival of immunized mice after challenge with T. gondii. ELISPOT analysis was used for the experimental testing of peptide immunogenicity.RESULTS: Predictions for the Db MHC-I molecule produced a strong, negative correlation between survival and the dissociation constant of vaccine-derived peptides. The in silico analyses of nine T. gondii antigens identified peptides with a predicted dissociation constant in the interval from 10nM to 40μM. ELISPOT assays with splenocytes from T. gondii-infected mice further supported the importance of the peptide affinity for MHC-I.CONCLUSIONS: In silico analysis clearly helped the search for protective vaccine antigens. The ELISPOT analysis confirmed that the predicted T-cell epitopes were immunogenic by their ability to release interferon gamma in spleen cells.

U2 - 10.1016/j.ijid.2016.04.014

DO - 10.1016/j.ijid.2016.04.014

M3 - Journal article

C2 - 27109108

VL - 48

SP - 14

EP - 19

JO - International Journal of Infectious Diseases

JF - International Journal of Infectious Diseases

SN - 1201-9712

ER -