Diversity at the variable-joining region boundary of lambda light chains has a pronounced effect on immunoglobulin ligand-binding activity.

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Abstract
By recombining .lambda. light (L) chains having known variable (V) region amino acid or nucleotide sequences with a heavy (H) chain from a myeloma protein or a monoclonal antibody, reconstituted Ig that differed from each other in sequence by only one or a few amino acid substitutions at known L chain positions were obtained. Differences in affinity of the reconstituted Ig for 2,4-dinitrophenyl (DNP) ligands revealed a pronounced effect on Ig binding activity of amino acids at the V-J boundary of the .lambda. chains. In 1 instance, 2 reconstituted Ig that differed .apprx. 1000-fold in affinity for .epsilon.-DNP-aminocaproate differed in primary structure by only a single tyrosine-phenylalanine substitution at the V-J junction (position 98) of their .lambda. 2 chains, i.e., by only 1 of .apprx. 660 amino acid residues (L + H chains). By focusing on affinity changes, chains with unusual V.lambda.-J.lambda. junctional residues were identified. It is possible that because of a critical effect on tertiary structure junctional amino acid variations arising from gene segment assembly (V/J and perhaps V/D/J) constitute an important source of ligand-binding diversity of antibodies.