Self-association of human immunoglobulin kappa I light chains: role of the third hypervariable region.

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Abstract
Gel electrophoresis and molecular seive chromatography were used to compare 17 different human .kappa.I type Bence Jones proteins including 5 for which the amino acid sequence is known. Although electrophoresis in the presence of NaDodSO4 showed uniformity of covalent dimer and monomer MW, Sephadex chromatography under nondissociating conditions showed that monomers eluted with different apparent MW. These differences were attributed to heterogeneity in L chain self-association; dimerization constants of their behavior upon gel filtration ranged from < 103 to > 106 M-1. The variable region, more specifically the 3rd hypervariable region, appears to be responsible for the variation in the dimerization constant. Association properties of L chains of known sequence suggest that the presence of an aromatic or hydrophobic residue at position 96 enhances dimer formation whereas a charged residue at that position results in L chains remaining stable monomers. The location of hypervariable residue 96 within the amino-terminal portion of the joining segment of the variable region suggested that the joining region may account for the variability of self-association of L chains and that is has a function in determining the selective association of immunoglobulin polypeptide chains.