Gorny M K, Xu J Y, Gianakakos V, Karwowska S, Williams C, Sheppard H W, Hanson C V, Zolla-Pazner S
Department of Pathology, New York University Medical Center, NY 10016.
Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3238-42. doi: 10.1073/pnas.88.8.3238.
Cell lines secreting IgG1 human monoclonal antibodies (mAb) 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 HIVMN in vitro at nanogram levels, and bear the characteristics of antibodies associated with protective immunity in vivo.
通过对感染人类免疫缺陷病毒（HIV）个体的外周血细胞进行转化，并将转化后的细胞与一种人 - 鼠异源骨髓瘤细胞系（SHM - D33）融合，已产生了分泌针对HIV包膜糖蛋白gp120的IgG1人单克隆抗体（mAb）的细胞系。借助一段跨越HIV MN株gp120第三个可变结构域部分的23聚体合成肽，对两种人mAb进行了位点选择。这两种异源杂交瘤产生的IgG比其亲本淋巴母细胞系多三倍。这些mAb的特异性已分别定位到gp120第三个可变结构域二硫键环末端附近的序列Lys - Arg - Ile - His - Ile和His - Ile - Gly - Pro - Gly - Arg。这些mAb的解离常数分别为3.7×10⁻⁶ M和8.3×10⁻⁷ M，在纳克水平下可在体外中和HIVMN，并具有与体内保护性免疫相关的抗体特征。
