HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Agadjanyan, M. G. Articles by Weiner, D. B. Search for Related Content PubMed PubMed Citation Articles by Agadjanyan, M. G. Articles by Weiner, D. B.

Costimulatory Molecule Immune Enhancement in a Plasmid Vaccine Model Is Regulated in Part Through the Ig Constant-Like Domain of CD80/86 ¹

Michael G. Agadjanyan^*,, Michael A. 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^¶ and David B. Weiner^2,*

^* Department of Pathology and Laboratory Medicine, University of Pennsylvania, School of Medicine, and The Wistar Institute, Philadelphia, PA 19104; Institute for Molecular Medicine, Huntington Beach, CA 92649; Department of Surgery, University of Illinois, Chicago, IL 60612; and ^¶ Centre de Recherche du Centre hospitalier de l’Université de Montréal, Montreal, Québec, Canada

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.

This article has been cited by other articles:

				E. Bolesta, A. Kowalczyk, A. Wierzbicki, C. Eppolito, Y. Kaneko, M. Takiguchi, L. Stamatatos, P. A. Shrikant, and D. Kozbor Increased Level and Longevity of Protective Immune Responses Induced by DNA Vaccine Expressing the HIV-1 Env Glycoprotein when Combined with IL-21 and IL-15 Gene Delivery J. Immunol., July 1, 2006; 177(1): 177 - 191. [Abstract] [Full Text] [PDF]