The geometry of synthetic peptide-based immunogens affects the efficiency of T cell stimulation by professional antigen-presenting cells

In the pathway leading to antibody production there are two points at which CD4(+) T-h cells need to be recruited. The first of these is priming of T cells by their interaction with dendritic cells (DC) bearing antigen presen ted on MHC class II molecules and the second is the collaborative interacti on of these primed T cells with B cells presenting the same antigen. We hav e previously shown that the configuration of T and B cell determinants with in synthetic peptide immunogens can greatly influence the amount of immunog en required to produce an antibody response. Here we investigate whether th e difference in potency of different immunogens is related to their ability to be presented by either DC or B cells. We show that determinants in a br anched configuration, which are the most efficient at eliciting antibody in vivo, are presented to T cell clones by splenic CD8(-) DC 10-fold more eff iciently than the corresponding determinants in a tandem linear arrangement . B cells also showed preferential presentation of branched immunogens to o ne T cell clone but in contrast to DC, not to a second T cell clone, indica ting differences between the two antigen-presenting cell types. We also sho w that branched immunogens have a greater stability in serum compared to li near peptides, which may further enhance the differences in their in vivo p otency.