Mariani S M, Armandola E A, Ferrone S
Department of Microbiology and Immunology, New York Medical College, Valhalla 10595.
J Immunol. 1991 Aug 15;147(4):1322-30.
Four hundred and sixty-six hybridomas were generated from a BALB/c mouse immunized with the syngeneic anti-idiotypic mAb F5-830 that recognizes an idiotope in the Ag-combining site of mAb AC1.59. At an appropriate concentration, the latter reacts with a determinant expressed by HLA-DR1, DRw8, and DRw9 Ag and subtypes of HLA-DR4 and DRw6 allospecificities. Serologic and immunochemical assays identified eight anti-HLA-DR anti-anti-idiotypic mAb. They are heterogeneous in their reactivity with a panel of HLA-typed B lymphoid cells: like mAb AC1.59, the anti-anti-idiotypic mAb MA1/38, MA1/40, MA1/47, and MA1/98 recognize the determinant shared by HLA-DR1, DRw8, and DRw9 Ag and subtypes of HLA-DR4 Ag. On the other hand, the anti-anti-idiotypic mAb MA1/52, MA1/157, MA1/281, and MA1/285 have a more restricted reactivity, inasmuch as the corresponding determinant(s) is detectable on only some of the allospecificities recognized by mAb AC1.59. Each anti-anti-idiotypic mAb varies in its extent of reactivity with HLA-DR allospecificities. These results suggest differences in the fine specificity of anti-HLA-DR anti-anti-idiotypic mAb and in the structural characteristics of the mAb AC1.59 defined determinant shared by HLA-DR1, DRw8, and DRw9 Ag and subtypes of DR4 allospecificities. Furthermore, the anti-anti-idiotypic mAb are heterogeneous in terms of expression of idiotopes and of their spatial relationship with their Ag-combining site. The heterogeneity in the characteristics of anti-HLA-DR antibodies elicited with anti-idiotypic mAb F5-830 suggests that the Id cascade triggered by immunization with incompatible HLA allospecificities may account for the changes in the anti-HLA antibody specificity that have been observed in the course of an immune response to mismatched HLA alloantigens.
用识别单克隆抗体AC1.59抗原结合位点上一个独特型表位的同基因抗独特型单克隆抗体F5 - 830免疫BALB/c小鼠，产生了466个杂交瘤。在适当浓度下，后者与由HLA - DR1、DRw8、DRw9抗原以及HLA - DR4和DRw6同种特异性亚型所表达的一个决定簇发生反应。血清学和免疫化学分析鉴定出8种抗HLA - DR抗抗独特型单克隆抗体。它们与一组经HLA分型的B淋巴细胞的反应性各不相同：与单克隆抗体AC1.59一样，抗抗独特型单克隆抗体MA1/38、MA1/40、MA1/47和MA1/98识别HLA - DR1、DRw8、DRw9抗原以及HLA - DR4抗原亚型所共有的决定簇。另一方面，抗抗独特型单克隆抗体MA1/52、MA1/157、MA1/281和MA1/285的反应性更为局限，因为相应的决定簇仅在单克隆抗体AC1.59所识别的部分同种特异性上可检测到。每种抗抗独特型单克隆抗体与HLA - DR同种特异性的反应程度各不相同。这些结果表明抗HLA - DR抗抗独特型单克隆抗体的精细特异性以及由HLA - DR1、DRw8、DRw9抗原和DR4同种特异性亚型所共有的单克隆抗体AC1.59定义决定簇的结构特征存在差异。此外，抗抗独特型单克隆抗体在独特型表位的表达及其与抗原结合位点的空间关系方面也各不相同。用抗独特型单克隆抗体F5 - 830引发的抗HLA - DR抗体特征的异质性表明，由不相容的HLA同种特异性免疫接种引发的独特型级联反应可能解释了在对不匹配的HLA同种抗原的免疫反应过程中所观察到的抗HLA抗体特异性的变化。
