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

J. Biol. Chem., Vol. 279, Issue 48, 50257-50266, November 26, 2004

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 279/48/50257    most recent M405738200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend 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 Thai, R. Articles by Léonetti, M. Search for Related Content PubMed PubMed Citation Articles by Thai, R. Articles by Léonetti, M. Social Bookmarking                      What's this?

Antigen Stability Controls Antigen Presentation^*

Robert Thai, Gervaise Moine, Michel Desmadril, Denis Servent, Jean-Luc Tarride, André Ménez, and Michel Léonetti¶

From the Département d'Ingénierie et d'Etudes des Protéines, Commissariat à l'Energie Atomique, C.E. Saclay, 91191 Gif-sur-Yvette, France, and Laboratoire de Modélisation et d'Ingénierie des Protéines, EP1088 Université de Paris-Sud, F-91405 Orsay, France

We investigated whether protein stability controls antigen presentation using a four disulfide-containing snake toxin and three derivatives carrying one or two mutations (L1A, L1A/H4Y, and H4Y). These mutations were anticipated to increase (H4Y) or decrease (L1A) the antigen non-covalent stabilizing interactions, H4Y being naturally and frequently observed in neurotoxins. The chemically synthesized derivatives shared similar three-dimensional structure, biological activity, and T epitope pattern. However, they displayed differential thermal unfolding capacities, ranging from 65 to 98 °C. Using these differentially stable derivatives, we demonstrated that antigen stability controls antigen proteolysis, antigen processing in antigen-presenting cells, T cell stimulation, and kinetics of expression of T cell determinants. Therefore, non-covalent interactions that control the unfolding capacity of an antigen are key parameters in the efficacy of antigen presentation. By affecting the stabilizing interaction network of proteins, some natural mutations may modulate the subsequent T-cell stimulation and might help microorganisms to escape the immune response.

Received for publication, May 24, 2004 , and in revised form, August 3, 2004.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains a supplemental figure.

^¶ To whom correspondence should be addressed: Batiment 152, Département d'Ingénierie et d'Etudes des Protéines (DIEP) C.E. Saclay, 91191 Gif-sur-Yvette CEDEX, France. Tel.: 0169086456; Fax: 0169089071; E-mail: michel.leonetti{at}cea.fr.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				T. R. Dagenais, K. P. Demick, J. D. Bangs, K. T. Forest, D. M. Paulnock, and J. M. Mansfield T-Cell Responses to the Trypanosome Variant Surface Glycoprotein Are Not Limited to Hypervariable Subregions Infect. Immun., January 1, 2009; 77(1): 141 - 151. [Abstract] [Full Text] [PDF]

				M. Flobakk, I. B. Rasmussen, E. Lunde, T. Frigstad, G. Berntzen, T. E. Michaelsen, B. Bogen, and I. Sandlie Processing of an Antigenic Sequence from IgG Constant Domains for Presentation by MHC Class II J. Immunol., November 15, 2008; 181(10): 7062 - 7072. [Abstract] [Full Text] [PDF]

				N. Moretto, A. Bolchi, C. Rivetti, B. P. Imbimbo, G. Villetti, V. Pietrini, L. Polonelli, S. Del Signore, K. M. Smith, R. J. Ferrante, et al. Conformation-sensitive Antibodies against Alzheimer Amyloid-beta by Immunization with a Thioredoxin-constrained B-cell Epitope Peptide J. Biol. Chem., April 13, 2007; 282(15): 11436 - 11445. [Abstract] [Full Text] [PDF]

				L. Delamarre, R. Couture, I. Mellman, and E. S. Trombetta Enhancing immunogenicity by limiting susceptibility to lysosomal proteolysis J. Exp. Med., September 4, 2006; 203(9): 2049 - 2055. [Abstract] [Full Text] [PDF]

				L. S. Jones, L. J. Peek, J. Power, A. Markham, B. Yazzie, and C. R. Middaugh Effects of Adsorption to Aluminum Salt Adjuvants on the Structure and Stability of Model Protein Antigens J. Biol. Chem., April 8, 2005; 280(14): 13406 - 13414. [Abstract] [Full Text] [PDF]