Hartman A B, Mallett C P, Sheriff S, Smith-Gill S J
Department of Biologics Research, Walter Reed Army Institute, Washington, DC 20307.
J Immunol. 1988 Aug 1;141(3):932-6.
Nucleotide sequences of HyHEL-5, an antibody specific for chicken lysozyme (HEL), indicated unusual joins in the third complementarity-determining region of both the H and L chains. The VK-JK recombination site is unusual in that codon 96, normally derived from the JK gene segment, is deleted entirely, making the L3 one amino acid shorter than normal. Examination of the HyHEL-5 Fab-HEL x-ray structure suggests that the conformation of L3 is clearly important for Ag specificity. A comparison of the HyHEL-5 L3 with that of the structurally related antibody J539 indicates that the deleted residue significantly alters the conformation of the L3 turn. The H chain VH-DH join is also unusual; the VH junction site has probably occurred between the second and third nucleotides of codon 92, with the addition of five random nucleotides that encode for unusual amino acids Leu93 and His94. Although the conformation of H3 is different from what would be predicted from other H3 conformations and is clearly important to the complementarity of HyHEL-5 to HEL, the specific residues at the VH-DH join do not appear to directly contribute to Ag binding. It is not possible to attribute the main chain conformation of H3 to the particular sequence produced by the join; the structural features of H3 may be due to interactions with HEL and/or with other antibody residues.
HyHEL-5是一种针对鸡溶菌酶（HEL）的特异性抗体，其核苷酸序列表明，重链和轻链的第三个互补决定区存在异常连接。VK-JK重组位点不同寻常，因为通常来自JK基因片段的第96位密码子完全缺失，使得轻链第三互补决定区（L3）比正常情况短一个氨基酸。对HyHEL-5 Fab-HEL X射线结构的研究表明，L3的构象对抗原特异性显然很重要。将HyHEL-5的L3与结构相关抗体J539的L3进行比较，结果表明缺失的残基显著改变了L3转角的构象。重链VH-DH连接也不同寻常；VH连接位点可能发生在第92位密码子的第二个和第三个核苷酸之间，并添加了五个随机核苷酸，编码异常氨基酸Leu93和His94。尽管H3的构象与根据其他H3构象预测的不同，且显然对HyHEL-5与HEL的互补性很重要，但VH-DH连接处的特定残基似乎并未直接促成抗原结合。无法将H3的主链构象归因于连接产生的特定序列；H3的结构特征可能是由于与HEL和/或其他抗体残基的相互作用。
