Annis D S, Murphy-Ullrich J E, Mosher D F
Department of Medicine, University of Wisconsin, Madison, WI 53706, USA.
J Thromb Haemost. 2006 Feb;4(2):459-68. doi: 10.1111/j.1538-7836.2006.01723.x.
Thrombospondin-1 (TSP-1) has been implicated in many different processes based in part on inhibitory activities of anti-TSP-1 monoclonal antibodies (mAbs).
To map epitopes of 13 anti-TSP-1 mAbs to individual modules or groups of modules spanning TSP-1 and the closely related TSP-2 homolog.
The mapping has led to assignment or reassignment of the epitopes of four mAbs, refinement of the epitopes of six mAbs, and confirmation of the epitopes of the remaining three mAbs. ESTs10, P12, and MA-II map to the N-terminal domain; 5G11, TSP127.6, and ESTs12 to the third properdin module; C6.7, HB8432, and P10 to epidermal growth factor (EGF)-like modules 1 and/or 2; and A6.1, mAb133, MA-I, and D4.6 to the calcium-binding wire module. A6.1, which recognizes a region of the wire that is identical in mouse and human TSP-1, reacts with TSP-1 from both species, and also reacts weakly with human TSP-2. Two other mouse antihuman TSP-1 mAbs, A4.1 and D4.6, also react with mouse TSP-1.
Consideration of previous literature and mapping of epitopes of inhibitory mAbs suggest that biological activities are present throughout TSP-1, including the EGF-like modules that have not been implicated in the past. Because the epitopes for 10 of the antibodies likely are within 18 nm of one another in calcium-replete TSP-1, some of the inhibitory effects may result from steric hindrance. Such seems to be the case for mAb133, which binds the calcium-binding wire but is still able to interfere with the activation of latent TGF-beta by the properdin modules.
血小板反应蛋白-1（TSP-1）参与了许多不同的过程，部分原因是抗TSP-1单克隆抗体（mAb）具有抑制活性。
将13种抗TSP-1 mAb的表位定位到跨越TSP-1和密切相关的TSP-2同源物的单个模块或模块组。
通过定位，确定或重新确定了4种mAb的表位，细化了6种mAb的表位，并确认了其余3种mAb的表位。ESTs10、P12和MA-II定位到N端结构域；5G11、TSP127.6和ESTs12定位到第三个备解素模块；C6.7、HB8432和P10定位到表皮生长因子（EGF）样模块1和/或2；A6.1、mAb133、MA-I和D4.6定位到钙结合丝模块。A6.1识别小鼠和人TSP-1中相同的丝区域，与两种物种的TSP-1反应，也与人TSP-2弱反应。另外两种小鼠抗人TSP-1 mAb，A4.1和D4.6，也与小鼠TSP-1反应。
考虑先前的文献以及抑制性mAb表位的定位表明，TSP-1全序列都具有生物学活性，包括过去未涉及的EGF样模块。由于在富含钙的TSP-1中，10种抗体的表位可能彼此相距在18纳米以内，因此一些抑制作用可能是由于空间位阻。mAb133似乎就是这种情况，它结合钙结合丝，但仍能干扰备解素模块对潜伏TGF-β的激活。
