International Immunology, Vol 10, 1111-1119, Copyright © 1998 by Oxford University Press
C Sedlik, M Rojas and C Leclerc
Many antigens encountered by the immune system are included in complex
structures such as bacteria or parasites. We previously developed an in
vivo model to study the immunogenicity of particulate antigens, based on
covalent linkage of proteins or peptides to 1 microm latex particles and
showed that these antigens cannot be presented to MHC class II- restricted
specific T cells by B cells. However, they induce strong CD4+ T cell
responses when injected to mice without adjuvant. The present study
demonstrates that four out of the five proteins tested did not stimulate
antibody synthesis when linked to 1 microm microparticles, although a
strong IgG production was induced by the same proteins administered in
soluble form with adjuvant. In contrast, lysozyme and two synthetic
peptides containing B and T cell viral epitopes induced strong and
long-lasting specific antibody responses when linked to 1 micrometer
synthetic beads. The isotypic pattern of antibodies induced by particulate
lysozyme was similar to that induced by the soluble protein in alum.
Studies using CD4+ T cell-depleted mice revealed that the induction of
antibodies by particulate lysozyme strictly required Th cell activity.
Moreover, the T-B cell cooperation involved in B cell activation by
antigens linked to beads required CD40- CD40 ligand interaction. Thus,
these particulate antigens provide a useful tool to study the mechanisms of
induction of antibody response against complex bacterial or parasitic
antigens. Moreover, they may represent attractive candidates to elaborate
efficient new vaccines using short synthetic peptides.
ARTICLES
Activation of B cells by 1 microm particulate lysozyme or peptides: a Th-dependent pathway requiring CD40-CD40 ligand interaction
Unite de Biologie des Regulations Immunitaires, Institut Pasteur, Paris, France.
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