Antibodies to the superantigenic site of HIV-1 gp120: hydrolytic and binding activities of the light chain subunit.
Antibodies to the superantigenic site of HIV-1 gp120: hydrolytic and binding activities of the light chain subunit.
复制标题
HIV-1 gp120 超抗原位点的抗体：轻链亚基的水解和结合活性。
DOI：
10.1016/j.molimm.2006.12.005
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发表时间：
2007
影响因子：
3.6
通讯作者：
Paul,Sudhir
中科院分区：
文献类型：
--
作者：
Nishiyama,Yasuhiro;Karle,Sangeeta;Planque,Stephanie;Taguchi,Hiroaki;Paul,Sudhir
Antibodies (Abs) to the superantigenic determinant of HIV gp120 (gp120SAg) are potential protective agents against HIV infection. We report that the light chain subunits of Abs cloned from lupus patients using phage library methods bind and hydrolyze gp120SAgindependent of the heavy chain. Unlike frequent gp120SAgrecognition by intact Abs attributable to VHdomain structural elements, the isolated light chains expressed this activity rarely. Four light chains capable of gp120SAgrecognition were identified by fractionating phage displayed light chains using peptide probes containing gp120 residues 421–433, a gp120SAgcomponent. Three light chains expressed non-covalent gp120SAgbinding and one expressed gp120SAghydrolyzing activity. The hydrolytic light chain was isolated by covalent phage fractionation using an electrophilic analog of residues 421–433. This light chain hydrolyzed a reporter gp120SAgsubstrate and full-length gp120. Other peptide substrates and proteins were hydrolyzed at lower rates or not at all. Consistent with the expected nucleophilic mechanism of hydrolysis, the light chain reacted selectively and covalently with the electrophilic gp120SAgpeptide analog. The hydrolytic reaction entailed a fast initial step followed by a slower rate limiting step, suggesting rapid substrate acylation and slow deacylation. All four gp120SAg-recognizing light chains contained sequence diversifications relative to their germline gene counterparts. These observations indicate that in rare instances, the light chain subunit can bind and hydrolyze gp120SAgwithout the participation of the heavy chain. The pairing of such light chains with heavy chains capable of gp120SAgrecognition represents a potential mechanism for generating protective Abs with enhanced HIV binding strength and anti-viral proteolytic activity.
