Costimulatory molecule immune enhancement in a plasmid vaccine model is regulated in part through the Ig constant-like domain of CD80/861

Michael G. Agadjanyan, Michael Anand Chattergoon, Mark J. Holterman, Behjatolah Monzavi-Karbassi, J. Joseph Kim, Tzvete Dentchev, Darren Wilson, Velpandi Ayyavoo, Luis J. Montaner, Thomas Kieber-Emmons, Rafick P. Sekaly, David B. Weiner

Research output: Contribution to journalArticle

Abstract

There is great interest in understanding the role of costimulatory molecules in immune activation. In both the influenza and HIV DNA immunization models, several groups have reported that coimmunization of mice with plasmids encoding immunogen and CD86, but not CD80, effectively boosts Ag-specific T cell activation. This difference in immune priming provided an opportunity to examine the functional importance of different regions of the B.7 molecules in immune activation. To examine this issue, we developed a series of chimeric CD80 and CD86 constructs as well as deletion mutants, and examined their immune activating potential in the DNA vaccine model. We demonstrate that the lack of an Ig constant-like region in the CD80 molecule is critically important to the enhanced immune activation observed. CD80 C-domain deletion mutants induce a highly inflammatory Ag-specific cellular response when administered as part of a plasmid vaccine. The data suggest that the constant-like domains, likely through intermolecular interactions, are critically important for immune regulation during costimulation and that engineered CD80/86 molecules represent more potent costimulatory molecules and may improve vaccine adjuvant efficacy.

Original languageEnglish (US)
Pages (from-to)4311-4319
Number of pages9
JournalJournal of Immunology
Volume171
Issue number8
StatePublished - Oct 15 2003
Externally publishedYes

Fingerprint

Immunoglobulin Constant Regions
Plasmids
Vaccines
DNA Vaccines
Human Influenza
Immunization
HIV
T-Lymphocytes
DNA
Immunoglobulin Domains

ASJC Scopus subject areas

  • Immunology

Cite this

Agadjanyan, M. G., Chattergoon, M. A., Holterman, M. J., Monzavi-Karbassi, B., Kim, J. J., Dentchev, T., ... Weiner, D. B. (2003). Costimulatory molecule immune enhancement in a plasmid vaccine model is regulated in part through the Ig constant-like domain of CD80/861. Journal of Immunology, 171(8), 4311-4319.

Costimulatory molecule immune enhancement in a plasmid vaccine model is regulated in part through the Ig constant-like domain of CD80/861. / Agadjanyan, Michael G.; Chattergoon, Michael Anand; Holterman, Mark J.; Monzavi-Karbassi, Behjatolah; Kim, J. Joseph; Dentchev, Tzvete; Wilson, Darren; Ayyavoo, Velpandi; Montaner, Luis J.; Kieber-Emmons, Thomas; Sekaly, Rafick P.; Weiner, David B.

In: Journal of Immunology, Vol. 171, No. 8, 15.10.2003, p. 4311-4319.

Research output: Contribution to journalArticle

Agadjanyan, MG, Chattergoon, MA, Holterman, MJ, Monzavi-Karbassi, B, Kim, JJ, Dentchev, T, Wilson, D, Ayyavoo, V, Montaner, LJ, Kieber-Emmons, T, Sekaly, RP & Weiner, DB 2003, 'Costimulatory molecule immune enhancement in a plasmid vaccine model is regulated in part through the Ig constant-like domain of CD80/861', Journal of Immunology, vol. 171, no. 8, pp. 4311-4319.
Agadjanyan, Michael G. ; Chattergoon, Michael Anand ; Holterman, Mark J. ; Monzavi-Karbassi, Behjatolah ; Kim, J. Joseph ; Dentchev, Tzvete ; Wilson, Darren ; Ayyavoo, Velpandi ; Montaner, Luis J. ; Kieber-Emmons, Thomas ; Sekaly, Rafick P. ; Weiner, David B. / Costimulatory molecule immune enhancement in a plasmid vaccine model is regulated in part through the Ig constant-like domain of CD80/861. In: Journal of Immunology. 2003 ; Vol. 171, No. 8. pp. 4311-4319.
@article{d036370bbb2641e598c29e0459c755d3,
title = "Costimulatory molecule immune enhancement in a plasmid vaccine model is regulated in part through the Ig constant-like domain of CD80/861",
abstract = "There is great interest in understanding the role of costimulatory molecules in immune activation. In both the influenza and HIV DNA immunization models, several groups have reported that coimmunization of mice with plasmids encoding immunogen and CD86, but not CD80, effectively boosts Ag-specific T cell activation. This difference in immune priming provided an opportunity to examine the functional importance of different regions of the B.7 molecules in immune activation. To examine this issue, we developed a series of chimeric CD80 and CD86 constructs as well as deletion mutants, and examined their immune activating potential in the DNA vaccine model. We demonstrate that the lack of an Ig constant-like region in the CD80 molecule is critically important to the enhanced immune activation observed. CD80 C-domain deletion mutants induce a highly inflammatory Ag-specific cellular response when administered as part of a plasmid vaccine. The data suggest that the constant-like domains, likely through intermolecular interactions, are critically important for immune regulation during costimulation and that engineered CD80/86 molecules represent more potent costimulatory molecules and may improve vaccine adjuvant efficacy.",
author = "Agadjanyan, {Michael G.} and Chattergoon, {Michael Anand} and Holterman, {Mark J.} and Behjatolah Monzavi-Karbassi and Kim, {J. Joseph} and Tzvete Dentchev and Darren Wilson and Velpandi Ayyavoo and Montaner, {Luis J.} and Thomas Kieber-Emmons and Sekaly, {Rafick P.} and Weiner, {David B.}",
year = "2003",
month = "10",
day = "15",
language = "English (US)",
volume = "171",
pages = "4311--4319",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "8",

}

TY - JOUR

T1 - Costimulatory molecule immune enhancement in a plasmid vaccine model is regulated in part through the Ig constant-like domain of CD80/861

AU - Agadjanyan, Michael G.

AU - Chattergoon, Michael Anand

AU - Holterman, Mark J.

AU - Monzavi-Karbassi, Behjatolah

AU - Kim, J. Joseph

AU - Dentchev, Tzvete

AU - Wilson, Darren

AU - Ayyavoo, Velpandi

AU - Montaner, Luis J.

AU - Kieber-Emmons, Thomas

AU - Sekaly, Rafick P.

AU - Weiner, David B.

PY - 2003/10/15

Y1 - 2003/10/15

N2 - There is great interest in understanding the role of costimulatory molecules in immune activation. In both the influenza and HIV DNA immunization models, several groups have reported that coimmunization of mice with plasmids encoding immunogen and CD86, but not CD80, effectively boosts Ag-specific T cell activation. This difference in immune priming provided an opportunity to examine the functional importance of different regions of the B.7 molecules in immune activation. To examine this issue, we developed a series of chimeric CD80 and CD86 constructs as well as deletion mutants, and examined their immune activating potential in the DNA vaccine model. We demonstrate that the lack of an Ig constant-like region in the CD80 molecule is critically important to the enhanced immune activation observed. CD80 C-domain deletion mutants induce a highly inflammatory Ag-specific cellular response when administered as part of a plasmid vaccine. The data suggest that the constant-like domains, likely through intermolecular interactions, are critically important for immune regulation during costimulation and that engineered CD80/86 molecules represent more potent costimulatory molecules and may improve vaccine adjuvant efficacy.

AB - There is great interest in understanding the role of costimulatory molecules in immune activation. In both the influenza and HIV DNA immunization models, several groups have reported that coimmunization of mice with plasmids encoding immunogen and CD86, but not CD80, effectively boosts Ag-specific T cell activation. This difference in immune priming provided an opportunity to examine the functional importance of different regions of the B.7 molecules in immune activation. To examine this issue, we developed a series of chimeric CD80 and CD86 constructs as well as deletion mutants, and examined their immune activating potential in the DNA vaccine model. We demonstrate that the lack of an Ig constant-like region in the CD80 molecule is critically important to the enhanced immune activation observed. CD80 C-domain deletion mutants induce a highly inflammatory Ag-specific cellular response when administered as part of a plasmid vaccine. The data suggest that the constant-like domains, likely through intermolecular interactions, are critically important for immune regulation during costimulation and that engineered CD80/86 molecules represent more potent costimulatory molecules and may improve vaccine adjuvant efficacy.

UR - http://www.scopus.com/inward/record.url?scp=0141992845&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141992845&partnerID=8YFLogxK

M3 - Article

C2 - 14530356

AN - SCOPUS:0141992845

VL - 171

SP - 4311

EP - 4319

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 8

ER -