Clonal characterization of the human IgG antibody repertoire to Haemophilus influenzae type b polysaccharide: V. In vivo expression of individual antibody clones is dependent on Ig C_H haplotypes and the categories of antigen

Antibodies (Ab) to the polysaccharide capsule of Haemophilus influenzae type b (Hib-PS) provide protection against Haemophilus influenzae type b disease in children, and Hib-PS vaccines with different immunologie properties are widely used clinically. The repertoire of human anti-Hib-PSAb induced by these vaccines is relatively restricted and can be divided into two types by the structure of the light chain V region. Ab using A2-VΚll gene product, which account for the majority of anti-Hib-PSAb response in most patients, show little somatic mutations. In contrast, non-Ab using A2-VΚII gene product use V_L genes from the VΚII, VΚII, VΚIII, VΚIV, and V_λ subgroups, are variably expressed among patients, and contain somatic mutations. To further study the expression of these two types of anti-Hib-PS Ab, we have produced KB13, a mAb specific for VΚII subgroup, and used mAb specific for various other VL subgroups to develop immunoassays specific for anti-Hib-PS Ab of each V_L subgroup. When Ig allotypes were studied for the effect on the Ab repertoire, A2-VΚII (A2) Ab were found to be expressed less in patients expressing fb or zag C_H haplotypes (p < 0.05). When the T cell-independent Hib-PS carbohydrate vaccine was compared to two T cell-dependent Hib-PS protein conjugate vaccines for their effect on Ab repertoire, Ab using VΚIII V_L were found tobe more often elicited with the conjugate vaccines than with the Hib-PS carbohydrate vaccine ( p < 0.01 ). Thus, individual members of the anti-Hib-PS Ab repertoire differ not only in their V region structure but also in the control of their expression.