PRODUCTION OF SITE-SELECTED NEUTRALIZING HUMAN MONOCLONAL-ANTIBODIES AGAINST THE 3RD VARIABLE DOMAIN OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GLYCOPROTEIN
PRODUCTION OF SITE-SELECTED NEUTRALIZING HUMAN MONOCLONAL-ANTIBODIES AGAINST THE 3RD VARIABLE DOMAIN OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GLYCOPROTEIN
复制标题
DOI：
10.1073/pnas.88.8.3238
复制
发表时间：
1991-04-01
影响因子：
11.1
通讯作者：
ZOLLAPAZNER, S
中科院分区：
文献类型：
--
作者：
GORNY, MK;XU, JY;ZOLLAPAZNER, S
人类免疫缺陷病毒（HIV）包膜糖蛋白gp120分泌IgG1人单克隆抗体（mab）的细胞系是通过转化HIV感染者的外周血细胞并将转化的细胞与人-小鼠异骨髓瘤细胞系（SHM-D33）融合而产生的。两个人单克隆抗体是通过从HIV MN株中合成的一个23-mer的肽段，该肽段跨越了gp120的第三个可变结构域的一部分。这两个异杂交瘤产生的IgG是它们亲本淋巴母细胞样细胞系的三倍。这些单克隆抗体的特异性已被定位到gp120第三可变结构域二硫环顶端附近的序列，分别是Lys-Arg-Ile-His-Ile和hys - ile - gly - pro - gly - arg。该单抗的解离常数为3.7 X 10(-6) M和8.3 X 10(-7) M，在体外能在纳克水平上中和HIV(MN)，在体内具有与保护性免疫相关的抗体特征。
Cell lines secreting IgG1 human monoclonal antibodies (mAbs) to the envelope glycoprotein, gp120, of human immunodeficiency virus (HIV) have been produced by transformation of peripheral blood cells from HIV-infected individuals and by fusion of transformed cells to a human-mouse heteromyeloma cell line (SHM-D33). Two human mAbs were site-selected by means of a 23-mer synthetic peptide spanning a portion of the third variable domain of gp120 from the MN strain of HIV. The two heterohybridomas produce three times more IgG than do their parent lymphoblastoid cell lines. The specificities of these mAbs have been mapped to sequences near the tip of the disulfide loop of the gp120 third variable domain, Lys-Arg-Ile-His-Ile and His-Ile-Gly-Pro-Gly-Arg, respectively. The mAbs have dissociation constants of 3.7 X 10(-6) M and 8.3 X 10(-7) M, neutralize HIV(MN) in vitro at nanogram levels, and bear the characteristics of antibodies associated with protective immunity in vivo.