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 immunologic properties are widely used clinically. The repertoire of human anti-Hib-PS Ab 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-VκII gene product, which account for the majority of anti-Hib-PS Ab response in most patients, show little somatic mutations. In contrast, non-Ab using A2- VκII gene product use V(L) genes from the VκI, 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 V(κ)II subgroup, and used mAb specific for various other V(L) 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-V(κ)II(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 V(κ)IIIV(L) were found to be 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.