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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Léonetti, M. Articles by Ménez, A. Search for Related Content PubMed PubMed Citation Articles by Léonetti, M. Articles by Ménez, A.

Increasing Immunogenicity of Antigens Fused to Ig-Binding Proteins by Cell Surface Targeting

Département d’Ingéniérie et d’Études des Protéines (DIEP) C. E. Saclay, Gif-Sur-Yvette, France

Fusion of antigenic proteins to Ig-binding proteins such as protein A from Staphylococcus aureus and its derived ZZ fragment is known to increase immunogenicity of the fused Ag in vivo. To shed light on the origin of this effect, we used snake toxins as Ags and observed that 1) fusion of toxins to ZZ enhanced their presentation to a toxin-specific T cell hybridoma (T1B2), using A20 B lymphoma cells, splenocytes, or peritoneal exudate cells as APCs; 2) this enhancement further increased when the number of fused Ig-binding domains varied from two with ZZ to five with protein A; and 3) the phenomenon vanished when the fusion protein was preincubated with an excess of free ZZ or when P388D1 monocytes cells were used as APCs. Therefore, ZZ-fused toxins are likely to be targeted to surface Igs of APCs by their ZZ moiety. Furthermore, ZZ- and toxin stimulated similar profiles of toxin-specific T cells in BALB/c mice, suggesting a comparable processing and presentation in vivo for both toxin forms. To improve the targeting efficiency, ZZ- was noncovalently complexed to various Igs directed to different cell surface components of APCs. The resulting complexes were up to 10³-fold more potent than the free toxin at stimulating T1B2. Also, they elicited both a T cell and an Ab response in BALB/c mice, without the need of any adjuvant. This simple approach may find practical applications by increasing the immunogenicity of recombinant proteins without the use of adjuvant.

This article has been cited by other articles:

				L. Agren, E. Sverremark, L. Ekman, K. Schon, B. Lowenadler, C. Fernandez, and N. Lycke The ADP-Ribosylating CTA1-DD Adjuvant Enhances T Cell-Dependent and Independent Responses by Direct Action on B Cells Involving Anti-Apoptotic Bcl-2- and Germinal Center-Promoting Effects J. Immunol., June 15, 2000; 164(12): 6276 - 6286. [Abstract] [Full Text] [PDF]

				M. Leonetti, J. Galon, R. Thai, C. Sautes-Fridman, G. Moine, and A. Menez Presentation of Antigen in Immune Complexes Is Boosted by Soluble Bacterial Immunoglobulin Binding Proteins J. Exp. Med., April 19, 1999; 189(8): 1217 - 1228. [Abstract] [Full Text] [PDF]