This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tongren, J. E.
Right arrow Articles by Riley, E. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tongren, J. E.
Right arrow Articles by Riley, E. M.

 Previous Article  |  Next Article 

Infection and Immunity, December 2005, p. 8119-8129, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.8119-8129.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Epitope-Specific Regulation of Immunoglobulin Class Switching in Mice Immunized with Malarial Merozoite Surface Proteins

Jon Eric Tongren,1 Patrick H. Corran,1,2 William Jarra,3 Jean Langhorne,3 and Eleanor M. Riley1*

Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom,1 Immunobiology Division, National Institute for Biological Standards and Control, South Mimms, Herts EN6 3QG, United Kingdom,2 Division of Parasitology, National Institute for Medical Research, Mill Hill, London NW7 7AA, United Kingdom3

Received 8 July 2005/ Returned for modification 20 August 2005/ Accepted 21 September 2005

Antibodies that bind to Fc receptors and activate complement are implicated in the efficient control of pathogens, but the processes that regulate their induction are still not well understood. To investigate antigen-dependent factors that regulate class switching, we have developed an in vivo model of class switching to immunoglobulin G2b (IgG2b) using the malaria antigen Plasmodium falciparum merozoite surface protein 2 (MSP2). C57BL/6 mice were immunized with recombinant proteins representing discrete domains of MSP2, and a T-cell epitope (C8) was identified within the conserved C terminus of the protein that preferentially induces IgG2b antibodies. The ability of C8 to induce IgG2b is ablated in both homozygous gamma interferon-negative and interleukin 10-negative mice. The IgG2b-inducing properties of C8 override the IgG1-inducing properties of both the fusion protein partner, glutathione S-transferase, and the adjuvant. Furthermore, when attached to other proteins that normally induce IgG1 responses, C8 induces a switch to IgG2b secretion. This is the first description of a defined T-cell epitope that drives specific IgG2b subclass switching, and our data offer proof of the concept that chimeric vaccines incorporating specific T-cell "switch epitopes" might be used to enhance qualitative aspects of the antibody response.

* Corresponding author. Mailing address: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom. Phone: (44) 207 927 2706. Fax: (44) 207 927 2807. E-mail: eleanor.riley{at}lshtm.ac.uk.

Editor: W. A. Petri, Jr.

Infection and Immunity, December 2005, p. 8119-8129, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.8119-8129.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Stanisic, D. I., Richards, J. S., McCallum, F. J., Michon, P., King, C. L., Schoepflin, S., Gilson, P. R., Murphy, V. J., Anders, R. F., Mueller, I., Beeson, J. G. (2009). Immunoglobulin G Subclass-Specific Responses against Plasmodium falciparum Merozoite Antigens Are Associated with Control of Parasitemia and Protection from Symptomatic Illness. Infect. Immun. 77: 1165-1174 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»