title: Epitope-specific regulation of immunoglobulin class switching in mice immunized with malarial merozoite surface proteins.
abstract: 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.
authors.affiliation: Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom.
authors.forename: Jon Eric
authors.initials: JE
authors.lastname: Tongren
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Corran
authors.forename: William
authors.initials: W
authors.lastname: Jarra
authors.forename: Jean
authors.initials: J
authors.lastname: Langhorne
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Riley
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D049109:Cell Proliferation; D017124:Conserved Sequence; D016207:Cytokines / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006720:Homozygote; D007114:Immunization; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007074:Immunoglobulin G / Q000235:genetics* / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000276:immunology; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D013154:Spleen / Q000166:cytology
chemical_list: D000953:Antigens, Protozoan; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D010455:Peptides; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C065974:merozoite surface protein 2, Plasmodium; D016753:Interleukin-10; D007371:Interferon-gamma