Armandola E A, Mariani S M, Zwickl M, Hardman N, Ferrone S
Department of Microbiology and Immunology, New York Medical College, Valhalla 10595.
Eur J Immunol. 1992 Nov;22(11):2893-9. doi: 10.1002/eji.1830221121.
The structural organization of anti-idiotypic (id) antibodies has been investigated mostly in haptenic systems. No information is available about the structural characteristics of anti-id antibodies in major histocompatibility complex (MHC) antigenic systems, although these data may contribute to our understanding of the molecular basis of their functional role in the immune response. Therefore, we have determined the nucleotide and derived amino acid sequence of the VH and VL regions of the anti-id monoclonal antibodies (mAb) F5-444, F5-830, F5-963, F5-1126, F5-1336 and F5-1419, which had been elicited with the syngeneic anti-HLA-DR1, 4, w14, w8, 9 mAb AC1.59. The six anti-id mAb are heterogenous in their VH and VL region gene usage. This structural heterogeneity is not correlated with their target specificity and with their ability to elicit anti-HLA-DR antibodies. The latter characteristic is markedly influenced by a limited number of amino acid substitutions, since mAb F5-444, which induces anti-HLA-DR antibodies, differs only in two residues in complementarity-determining regions and in five residues in framework regions from mAb F5-1126, which does not induce anti-HLA-DR antibodies. The heterogeneity in VH and VL region gene usage by the six anti-id mAb in the HLA-DR system is at variance with the restricted VH and VL region gene usage by syngeneic anti-id mAb in several haptenic systems. Furthermore, at variance with haptenic systems, the primary structure of the D segments of the anti-id mAb is not correlated with their ability to induce anti-HLA-DR antibodies. On the other hand, the frequency of D-D fusion events underlying the derivation of the D segments of the six anti-id mAb in the HLA-DR system and their average length are similar to those found in anti-id mAb in haptenic systems. In addition, like in the latter systems, somatic mutations appear to contribute to the generation of diversity of anti-id mAb in the HLA-DR system.
抗独特型（Id）抗体的结构组织大多是在半抗原系统中进行研究的。关于主要组织相容性复合体（MHC）抗原系统中抗Id抗体的结构特征尚无相关信息，尽管这些数据可能有助于我们理解它们在免疫反应中功能作用的分子基础。因此，我们已经确定了抗Id单克隆抗体（mAb）F5-444、F5-830、F5-963、F5-1126、F5-1336和F5-1419的VH和VL区域的核苷酸及推导的氨基酸序列，这些抗体是由同基因抗HLA-DR1、4、w14、w8、9单克隆抗体AC1.59诱导产生的。这六种抗Id单克隆抗体在VH和VL区域基因使用上是异质的。这种结构异质性与其靶标特异性以及诱导抗HLA-DR抗体的能力无关。后一种特征受到有限数量氨基酸取代的显著影响，因为诱导抗HLA-DR抗体的单克隆抗体F5-444与不诱导抗HLA-DR抗体的单克隆抗体F5-1126相比，仅在互补决定区有两个残基不同，在框架区有五个残基不同。六种抗Id单克隆抗体在HLA-DR系统中VH和VL区域基因使用的异质性与几种半抗原系统中同基因抗Id单克隆抗体受限的VH和VL区域基因使用情况不同。此外，与半抗原系统不同，抗Id单克隆抗体D段的一级结构与其诱导抗HLA-DR抗体的能力无关。另一方面，HLA-DR系统中六种抗Id单克隆抗体D段推导过程中D-D融合事件的频率及其平均长度与半抗原系统中抗Id单克隆抗体的情况相似。此外，与后一种系统一样，体细胞突变似乎有助于HLA-DR系统中抗Id单克隆抗体多样性的产生。
