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 CH 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-V kappa II 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-V kappa II gene product use VL genes from the V kappa I, V kappa II, V kappa III, V kappa IV, and V lambda 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 kappa II subgroup, and used mAb specific for various other VL subgroups to develop immunoassays specific for anti-Hib-PS Ab of each VL subgroup. When Ig allotypes 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 zag CH 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 kappa III VL 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.
Chung
G H
GH
Washington University School of Medicine, Department of Pathology, St Louis, MO 63110.
Scott
M G
MG
Kim
K H
KH
Kearney
J
J
Siber
G R
GR
Ambrosino
D M
DM
Nahm
M H
MH
D000328:Adult; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000911:Antibodies, Monoclonal / Q000276:immunology; D016667:Bacterial Capsules; D018073:Haemophilus Vaccines / Q000276:immunology*; D006193:Haemophilus influenzae / Q000276:immunology*; D006239:Haplotypes; D006801:Humans; D007114:Immunization; D007126:Immunoglobulin Allotypes / Q000032:analysis; D007127:Immunoglobulin Constant Regions / Q000235:genetics*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D011863:Radioimmunoassay
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine; D007126:Immunoglobulin Allotypes; D007127:Immunoglobulin Constant Regions; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D011135:Polysaccharides, Bacterial