CLONAL CHARACTERIZATION OF THE HUMAN-IGG ANTIBODY REPERTOIRE TO HAEMOPHILUS-INFLUENZAE TYPE-B POLYSACCHARIDE .5. 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 influenza e type b (Hib-PS) provide protection against Haemophilus influenzae ty pe b disease in children, and Hib-PS vaccines with different immunolog ic 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-VkappaII gene product, which account for the majority of anti-Hib-PS Ab response in most patients, show little somatic mutatio ns. In contrast, non-Ab using A2-VkappaII gene product use V(L) genes from the VkappaI, VkappaII, VkappaIII, VkappaIV, and V(lambda) subgrou ps, are variably expressed among patients, and contain somatic mutatio ns. To further study the expression of these two types of anti-Hib-PS Ab, we have produced KB13, a mAb specific for V(kappa)II subgroup, and used mAb specific for various other V(L) subgroups to develop immunoa ssays specific for anti-Hib-PS Ab of each V(L) subgroup. When Ig allot ypes were studied for the effect on the Ab repertoire, A2-V(kappa)II ( A2) Ab were found to be expressed less in patients expressing fb or za g C(H) haplotypes (p < 0.05). When the T cell-independent Hib-PS carbo hydrate vaccine was compared to two T cell-dependent Hib-PS protein co njugate vaccines for their effect on Ab repertoire, Ab using V(kappa)I II V(L) were found to be more often elicited with the conjugate vaccin es than with the Hib-PS carbohydrate vaccine (p < 0.01). Thus, individ ual members of the anti-Hib-PS Ab repertoire differ not only in their V region structure but also in the control of their expression.