Diversity of immunoglobulin light chain usage in the human immune response to Haemophilus influenzae type b capsular polysaccharide.
The response to the capsular polysaccharide of Haemophilus influenzae type b (Hib PS) has been used to determine the molecular basis of antibody gene diversity in humans. In contrast to the relatively restricted nature of anti-Hib PS heavy-chain variable region gene expression, a variety of light-chain variable region genes may encode this antibody (Ab) response. Light-chain variable region gene usage appears to determine the expression of certain Ab idiotypes and fine antigen specificity. To further define the role of light-chain variable region gene usage in important anti-Hib PS Ab subgroups, we have cloned and sequenced a number of immunoglobulin light-chain variable region genes (IgVL) from human monoclonal IgA anti-Hib PS Ab generated in response to Hib PS-protein conjugate vaccines. Three of these Ab are encoded by unusual variable segments. One kappa-Ab is encoded by the "predominant" V kappa II A2 germline gene but, in contrast to a previously reported A2-encoded IgVL sequence, differs from the A2 germline sequence. The IgVL sequence of a second Ab is the only sequence of a kappa-Ab that cross-reacts with the structurally related antigen Escherichia coli K100 polysaccharide reported to date. This IgVL is encoded by a V kappa III-segment most closely homologous to the Humhv328/L16 germline gene, whereas previous reports suggested V kappa III-encoded anti-Hib PS Ab might be exclusively encoded by the germline gene Humhv325/A27.(ABSTRACT TRUNCATED AT 250 WORDS)
Adderson
E E
EE
Department of Pediatrics, University of Utah, Salt Lake City 84112.
Shackelford
P G
PG
Quinn
A
A
Wilson
P M
PM
Carroll
W L
WL
D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000235:genetics; D000911:Antibodies, Monoclonal; D000916:Antibody Diversity / Q000235:genetics*; D016667:Bacterial Capsules; D001428:Bacterial Vaccines / Q000276:immunology*; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D005803:Genes, Immunoglobulin; D018073:Haemophilus Vaccines; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D008969:Molecular Sequence Data; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D001428:Bacterial Vaccines; D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine; D007147:Immunoglobulin Light Chains; D011135:Polysaccharides, Bacterial; D004247:DNA