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II-A2 Light Chain CDR-3 Junctional Residues in Human Antibody Binding to the Haemophilus influenzae Type b Polysaccharide1
Children’s Hospital Oakland Research Institute, Oakland, CA 94609
Abs using the 
II-A2 V gene segment predominate the human Ab
repertoire to the Haemophilus influenzae b (Hib)
polysaccharide (PS). All A2 anti-Hib PS Abs sequenced to date
possess a 10-amino acid L chain complementarity-determining region-3
(CDR-3) having an insertional arginine (Arg) at position 95a, the V-J
junction. These findings suggest an essential requirement for this
conserved Arg residue in determining Hib PS-binding affinity. We
examined this requirement by performing chain recombination experiments
in which a series of A2 L chains, differing at position 95a, were
combined individually with an Fd region known to generate a Hib
PS-combining site when paired with an A2-Arg(95a)-J1 V region. Hib
PS binding of the recombinant Fabs was evaluated quantitatively using a
radioantigen-binding assay. Fabs having A2 L chains with either Arg or
lysine in position 95a in combination with J1 gave equivalent and
strongest binding to Hib PS. Fabs having A2-J1 L chains with either
tyrosine, glycine, alanine, leucine, serine, or threonine in position
95a, or having an A2-Arg(95a)-J3 L chain, gave intermediate binding.
Fabs having A2-J1 L chains with glutamate or aspartate at 95a or
with no junctional residue showed little or no Hib PS binding. These
results demonstrate the importance of L chain junctional residue, as
well as J usage and CDR-3 length, in determining Hib PS-binding
affinity. Contrary to expectation, an Arg junctional residue is not
essential for generating either high or intermediate affinity-binding
sites.
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