TY - JOUR
T1 - Structural basis for the preferential association of autologous immunoglobulin subunits
T2 - Role of the J region of the light chain
AU - Hamel, Paul A.
AU - Isenman, David E.
AU - Klein, Michel H.
AU - Luedtke, Robert
AU - Dorrington, Keith J.
PY - 1984/4
Y1 - 1984/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0021265798&partnerID=8YFLogxK
U2 - 10.1016/0161-5890(84)90098-1
DO - 10.1016/0161-5890(84)90098-1
M3 - Article
C2 - 6427603
AN - SCOPUS:0021265798
SN - 0161-5890
VL - 21
SP - 277
EP - 283
JO - Molecular Immunology
JF - Molecular Immunology
IS - 4
ER -