Correlation of antigenic epitope and antibody gene usage in the human immune response to Streptococcus pneumoniae type 23F capsular polysaccharide

The human antibody response to the capsular polysaccharide of Streptococcus pneumoniae type 23F is predominated by antibodies which express either VκL6 or VκA23 light chain genes. In this report, we demonstrate that the antigenic epitopes recognized by these two families can be differentiated based on their specificity for the hapten l-rhamnose, a constituent sugar of the bacterial capsule polymer. The VκL6 family utilizes light chains with an unusually long third complementarity-determining region. These VκL6-encoded Fabs are 100-fold more sensitive to inhibition with l-rhamnose than VκA23 Fabs. VκL6 Fabs preferentially recognize the l-isomer of the hapten and can distinguish l-rhamnose from the structurally similar sugar l-mannose. We also demonstrate that the VκL6 family component of the antibody response recognizes the polysaccharide antigens of Group B streptococci (GBS), thereby accounting for the previously reported cross-reaction between PPS 23F-specific antisera and Group B streptococci.