Cognate stimulatory B-cell-T-cell interactions are critical for T-cell help recruited by glycoconjugate vaccines

Covalent linkage of a bacterial polysaccharide to an immunogenic protein gr eatly enhances the carbohydrate's immunogenicity and induces polysaccharide -specific B-cell memory in vivo. These findings have spurred the developmen t of glycoconjugate vaccines for serious bacterial infections. The specific B-cell-T-cell interactions responsible for recruitment of T-cell help by g lycoconjugate vaccines are not well defined. We used mice deficient in mole cules critical for stimulatory, cognate B-cell-T-cell interactions to study how T cells improve the immunogenicity of a glycoconjugate vaccine against group B streptococcal disease. Isotype switching to immunoglobulin G (IgG) was abrogated in mice deficient in major histocompatibility complex (MHC) class II antigen (Ag)-T-cell receptor (TCR), B7-CD28, or CD40-CD40L interac tions. However, expression of either the B7-1 or the B7-2 molecule on antig en-presenting cells was sufficient for optimal T-cell costimulation. T cell s activated by the vaccine also played a pivotal role in determining the ma gnitude of the IgM response to the polysaccharide. Comparable results were obtained with pathway antagonists. These data suggest that MHC class II Ag- TCR, B7-CD28, and CD40-CD40L interactions are critical for immune responses to glycoconjugate vaccines in vivo.