Chia J K, Pollack M, Avigan D, Steinbach S
Infect Immun. 1986 Jun;52(3):756-62. doi: 10.1128/iai.52.3.756-762.1986.
Monoclonal antibodies (MAbs) are described which react with two discrete structural domains of Pseudomonas aeruginosa toxin A and which have two distinct functional profiles. The MAbs designated T3-1C7 and T4-1F2 reacted with a 46,000-dalton peptide similar to the putative B or binding fragment of toxin A. These antibodies neutralized the cytotoxic and lethal properties of toxin but had no effect on its ADP-ribosyl transferase activity. T4-1F2 interfered with the binding of toxin A to membrane receptors on mouse fibroblasts (L cells), although the epitope for the antibody appears to be distinct from the actual receptor binding site. The MAb designated T2-1H2 reacted with intact toxin A and with a cloned, enzymatically active carboxy-terminal polypeptide similar to the toxin A fragment. This MAb neutralized the ADP-ribosyl transferase activity of activated holotoxin and of the cloned peptide, but inhibited neither binding of toxin to membrane receptors nor its cytotoxic and lethal actions. The complementary specificity and function of these MAbs confirm the functional specialization of discrete structural domains within the toxin A molecule. Our findings suggest the greater antitoxic potential of antibodies that block binding, compared with those which inhibit the enzymatic activity of toxin A.
已描述了与铜绿假单胞菌毒素A的两个不同结构域发生反应且具有两种不同功能特性的单克隆抗体（MAb）。命名为T3-1C7和T4-1F2的单克隆抗体与一种46,000道尔顿的肽发生反应，该肽类似于毒素A假定的B或结合片段。这些抗体中和了毒素的细胞毒性和致死特性，但对其ADP-核糖基转移酶活性没有影响。T4-1F2干扰了毒素A与小鼠成纤维细胞（L细胞）上膜受体的结合，尽管该抗体的表位似乎与实际的受体结合位点不同。命名为T2-1H2的单克隆抗体与完整的毒素A以及与一种克隆的、具有酶活性的羧基末端多肽发生反应，该多肽类似于毒素A片段。这种单克隆抗体中和了活化的全毒素和克隆肽的ADP-核糖基转移酶活性，但既不抑制毒素与膜受体的结合，也不抑制其细胞毒性和致死作用。这些单克隆抗体的互补特异性和功能证实了毒素A分子内不同结构域的功能特化。我们的研究结果表明，与抑制毒素A酶活性的抗体相比，阻断结合的抗体具有更大的抗毒素潜力。
