Anti-idiotypes to monoclonal anti-H-2 antibodies—I. Contribution of isolated heavy and light chains to idiotype expression

Bluestone, Jeffrey A.; Metzger, J. J.; Knode, Marian C.; Ozato, Keiko; Sachs, David H.

doi:10.1016/0161-5890(82)90219-x

Cited by 10 publications

(1 citation statement)

References 18 publications

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“…We consider three nonexclusionary classes of heterogeneity (Fig. 2) (52)(53)(54). In other cases, even an idiotope consisting solely of residues from a single chain may be blocked by the unfavorable location of residues from the other chain.…”

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Dual conformations of an immunoglobulin light-chain dimer: heterogeneity of antigen specificity and idiotope profile may result from multiple variable-domain interaction mechanisms.

Stevens

Chang

Schiffer

1988

Proc. Natl. Acad. Sci. U.S.A.

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The structure of an immunoglobulin antigenbinding fragment (Fab) has been thought to be invariantly defined by well-coiserved 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.Crystallographic studies of antigen-binding fragments (Fabs) have indicated that the principal determinants of quaternary structure are highly conserved domain-domain interactions (1)(2)(3)(4)(5) and that functional diversity originates from residue alternations, insertions, and deletions in segments of the heavy (H)-and light (L)-chain variable (V) domains designated hypervariable or complementarity determining regions (6). Several analogous studies with light-chain dimers have also supported the monomorphic conformation concept (7-10). However, in two instances (11,12), the observed Bence Jones protein conformations were anomalous; V-V domain interactions were found that had not been observed in Fabs. Although the relationships between these V domains were of significant interest in terms of the physical chemistry of antibody domain interactions, the physiological implications of the structures of the light-chain dimers formed by proteins Rhe (11)

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confidence: 99%