Structural basis for the preferential association of autologous immunoglobulin subunits: Role of the J region of the light chain

Paul A. Hamel, David E. Isenman, Michel H. Klein, Robert T. Luedtke, Keith J. Dorrington

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

We have used a series of sequenced Vκ21 L-chains produced from murine myelomas to determine whether the V or J segment of the V region is responsible for dictating preferential recombination. In each competitive recombination, equimolar amounts of two different L-chains, selected on the basis of common V or J segments, were allowed to compete for a limiting amount of H-chain. It was found that the J segment of the L-chain was primarily responsible for dictating the ability of a chain to compete and that the nature of residue 96, the first residue of the J segment, was particularly important. Specifically, charged residues caused the L-chain to compete poorly against L-chains with hydrophobic side chains at this position. Furthermore, if Phe or, to a lesser extent, Tyr were present at position 96, the L-chain competed more successfully than chains with Trp-96 or Leu-96. This suggests that both the aromaticity and size of this residue were important factors in determining preferential recombination. It was also found that all other residues in VL were secondary to residue 96 in contributing to the ability of a chain to compete. Finally, unlike all previous studies, we observed a substantial number (64%) of preferred heterologous recombinations. These results are consistent with the hypothesis that the Vl and Vh gene rearrangements occur independently, thus resulting in random pairing of VH and VL domains.

Original languageEnglish
Pages (from-to)277-283
Number of pages7
JournalMolecular Immunology
Volume21
Issue number4
DOIs
StatePublished - 1 Jan 1984

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Immunoglobulin Subunits
Genetic Recombination
Light
Gene Rearrangement

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Hamel, Paul A. ; Isenman, David E. ; Klein, Michel H. ; Luedtke, Robert T. ; Dorrington, Keith J. / Structural basis for the preferential association of autologous immunoglobulin subunits : Role of the J region of the light chain. In: Molecular Immunology. 1984 ; Vol. 21, No. 4. pp. 277-283.
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Structural basis for the preferential association of autologous immunoglobulin subunits : Role of the J region of the light chain. / Hamel, Paul A.; Isenman, David E.; Klein, Michel H.; Luedtke, Robert T.; Dorrington, Keith J.

In: Molecular Immunology, Vol. 21, No. 4, 01.01.1984, p. 277-283.

Research output: Contribution to journalArticle

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