Dual conformations of an immunoglobulin light-chain dimer: heterogeneity of antigen specificity and idiotope profile may result from multiple variable-domain interaction mechanisms.
The structure of an immunoglobulin antigen-binding fragment (Fab) has been thought to be invariantly defined by well-conserved amino acid residues in the variable domains of the heavy and light chains. These conserved residues enable folding of the polypeptide segments into the characteristic immunoglobulin fold domains and are the major controllers of interactions between domains. However, crystallographic studies of some immunoglobulin light-chain dimers have suggested and the crystallographic structure of the Fab in an Fab-neuraminidase complex may have proven that antibodies are not restricted to a single, invariant relative positioning of the two variable domains. We propose that in some cases the detailed quaternary structural relationships between the variable domains of heavy and light chains are not restricted to those of the canonical Fab. It is unclear whether alterations of these relationships occur only after complex formation with antigen or, if in ligand-free solution, Fab conformers might coexist in relative concentrations determined by isomerization rates. In the latter case, antibody-presenting lymphocytes may be polyspecific, and the specificity of lymphocytes might be modulated by anti-idiotopic antibodies complexed to cell surface receptors. In either case, the idiotopic repertoire displayed by an antibody or lymphocyte surface receptor might be changed by the presence or absence of antigen.
D000916:Antibody Diversity; D003196:Computer Graphics; D003461:Crystallography; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000032:analysis; D007130:Immunoglobulin Idiotypes; D007147:Immunoglobulin Light Chains / Q000032:analysis*; D046911:Macromolecular Substances; D009439:Neuraminidase / Q000378:metabolism; D011487:Protein Conformation
D007140:Immunoglobulin Fab Fragments; D007130:Immunoglobulin Idiotypes; D007147:Immunoglobulin Light Chains; D046911:Macromolecular Substances; D009439:Neuraminidase