Armandola E A, Mariani S M, Ferrone S
Department of Microbiology and Immunology, New York Medical College, Valhalla 10595.
Mol Immunol. 1993 Feb;30(3):287-300. doi: 10.1016/0161-5890(93)90057-i.
The molecular basis of the differential specificity of seven mouse anti-id mAb elicited with the syngeneic anti-HLA-A2,28 mAb CR11-351 was analyzed by comparing their specificity with their heavy and light chain variable region sequences. Of the six mAb recognizing idiotopes within the antigen combining site of mAb CR11-351, mAb T10-352, T10-440 and T10-505 recognize the same (or spatially close) idiotope(s) since they cross-inhibit each other in their binding to mAb CR11-351 and elicit syngeneic anti-anti-id antibodies with similar specificity. On the other hand, mAb T10-421, T10-649 and T10-938 appear to recognize spatially close but distinct idiotopes since they cross-inhibit each other, but elicit anti-anti-id antibodies which inhibit only the binding of the respective immunizing anti-id mAb to mAb CR11-351. mAb T8-203 is the only anti-id mAb which recognizes an idiotope outside the antigen combining site of mAb CR11-351 since it does not inhibit the binding of the latter to target cells and binds to mAb CR11-351 coated B lymphoid cells. In addition, mAb T8-203 defines an idiotope which is shared by seven anti-HLA mAb, while the remaining six anti-id mAb recognize idiotopes which are not detectable on the panel of anti-HLA mAb. mAb T10-352, T10-440 and T10-505 are highly homologous in their VH and VL regions and in their V(D)J junctions suggesting that they may be clonally related. On the other hand, mAb T8-203, T10-649 and T10-938 share some degree of homology in their VH region as all of them use J558 VH genes but differ considerably in their VL regions. Finally, mAb T10-421 is the most unrelated mAb as it utilizes VH, D, JH, VK and JK gene segments different from those of all the other anti-id mAb. These findings indicate that in the HLA-A antigenic system defined by mAb CR11-351 the main mechanism underlying the differential target specificity of syngeneic anti-id mAb is the combinatorial diversity together with the differential pairing of heavy and light chains.
通过比较七种同基因抗 HLA - A2,28 单克隆抗体（mAb）CR11 - 351 诱导产生的小鼠抗独特型单克隆抗体（anti - id mAb）的特异性与其重链和轻链可变区序列，分析了它们差异特异性的分子基础。在识别 mAb CR11 - 351 抗原结合位点内独特型表位的六种单克隆抗体中，mAb T10 - 352、T10 - 440 和 T10 - 505 识别相同（或空间上相近）的独特型表位，因为它们在与 mAb CR11 - 351 的结合中相互交叉抑制，并诱导产生具有相似特异性的同基因抗抗独特型抗体。另一方面，mAb T10 - 421、T10 - 649 和 T10 - 938 似乎识别空间上相近但不同的独特型表位，因为它们相互交叉抑制，但诱导产生的抗抗独特型抗体仅抑制相应免疫抗独特型单克隆抗体与 mAb CR11 - 351 的结合。mAb T8 - 203 是唯一一种识别 mAb CR11 - 351 抗原结合位点外独特型表位的抗独特型单克隆抗体，因为它不抑制后者与靶细胞的结合，且能与包被有 mAb CR11 - 351 的 B 淋巴细胞结合。此外，mAb T8 - 203 定义了一个由七种抗 HLA 单克隆抗体共享的独特型表位，而其余六种抗独特型单克隆抗体识别的独特型表位在抗 HLA 单克隆抗体组中无法检测到。mAb T10 - 352、T10 - 440 和 T10 - 505 在其 VH 和 VL 区域以及 V(D)J 连接区高度同源，表明它们可能是克隆相关的。另一方面，mAb T8 - 203、T10 - 649 和 T10 - 938 在其 VH 区域有一定程度的同源性，因为它们都使用 J558 VH 基因，但在 VL 区域差异较大。最后，mAb T10 - 421 是最不相关的单克隆抗体，因为它使用的 VH、D、JH、VK 和 JK 基因片段与所有其他抗独特型单克隆抗体不同。这些发现表明，在由 mAb CR11 - 351 定义的 HLA - A 抗原系统中，同基因抗独特型单克隆抗体差异靶特异性的主要机制是组合多样性以及重链和轻链的差异配对。
