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Structural determinants of the human idiotype HibId‐1
Author(s) -
Reason Donald C.,
O'Connor Adam P.,
Lucas Alexander H.
Publication year - 2001
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.548
Subject(s) - immunoglobulin light chain , idiotype , mutagenesis , biology , antibody , somatic hypermutation , streptococcus pneumoniae , gene , monoclonal antibody , mutation , microbiology and biotechnology , genetics , chemistry , bacteria , b cell
The human antibody response to the capsular polysaccharide of Haemophilus influenzae type b is predominated by antibodies expressing a light‐chain‐associated idiotype designated HibId‐1. HibId‐1 is expressed by κ light chains encoded by either the A2 or A18 variable region genes. In this report we use site‐directed mutagenesis and molecular modeling to show that HibId‐1 expression is determined by residues in the first and second complimentarity determining regions that are widely separated in the primary sequence, but closely juxtaposed by the tertiary folding of the mature light chain molecule. Of the known human light chains, only alleles of A2 and A18 encode these residues at these positions in their germline configuration. VIG10, a mouse monoclonal antibody of unknown specificity that expresses HibId‐1, and 23F.2, an A2‐utilizing Streptococcus pneumoniae 23F polysaccharide‐specific human Fab fragment that lacks HibId‐1, provide examples of the HibId‐1 determinant both arising and being lost by somatic mutation. In addition, we show that the residues responsible for HibId‐1 expression can be disassociated from those required for antigen binding. Copyright © 2001 John Wiley & Sons, Ltd.