Iwasaki Y, Takabatake H, Shinji T, Monestier M, Ferrone S
Department of Microbiology and Immunology, New York Medical College, Valhalla, NY 10595.
Eur J Immunol. 1994 Nov;24(11):2874-81. doi: 10.1002/eji.1830241144.
Interest in the characterization of idiotype cascades in the HLA antigenic system has been stimulated by their potential role in the immune response to mismatched HLA allospecificities and in the survival of kidney allografts. Since no information is available about the structural organization of idiotypic cascades in the HLA system, we have sequenced the variable regions of the heavy (VH) and light (VL) chains of mouse anti-HLA-DQ3 monoclonal antibody (mAb) KS13 elicited by cell membrane-bound antigens, of syngeneic anti-HLA-DQ3 mAb S2B154 elicited by anti-idiotypic (anti-id) mAb K03-34 and of five syngeneic anti-id mAb elicited by mAb KS13. mAb KS13 and S2B154, which have been previously shown to be very similar in their specificity and idiotypic profile, share several structural characteristics. Their VH and VL regions are encoded by the same VH, VK and JH genes, display relatively similar V(D)J rearrangements and differ only through a few amino acid substitutions. Among the five anti-id mAb elicited by mAb KS13, mAb R1-38 and R18-9 utilize multiple genetic elements that are different from those used by anti-id mAb KO3-34, K03-256 and K03-335. These results indicate that diverse V region combinations can confer an anti-id specificity in the antigenic system analyzed. mAb K03-34, K03-256 and K03-335 originate from the same B cell clone, since they use the same V, D and J genes and possess identical V(D)J rearrangements. The latter three anti-id mAb differ only by point mutations, which have dramatic effects on the HLA-DQ3 antigen mimicry properties of the three anti-id mAb. mAb K03-34 is the only one to induce anti-HLA-DQ3 antibodies both in syngeneic and xenogeneic hosts. The antigen mimicry properties of anti-id mAb K03-34 depend upon its three-dimensional conformation, since no significant amino acid sequence homology has been found between its VH and VL regions and alpha 1 and beta 1 domains of HLA-DQ3 antigens.
HLA抗原系统中独特型级联的特征研究受到了关注，因为它们在对不匹配的HLA同种特异性的免疫反应以及肾移植存活中可能发挥作用。由于目前尚无关于HLA系统中独特型级联结构组织的信息，我们对由细胞膜结合抗原诱导产生的小鼠抗HLA - DQ3单克隆抗体（mAb）KS13、由抗独特型（抗 - id）mAb K03 - 34诱导产生的同基因抗HLA - DQ3 mAb S2B154以及由mAb KS13诱导产生的五种同基因抗 - id mAb的重链（VH）和轻链（VL）可变区进行了测序。mAb KS13和S2B154先前已被证明在特异性和独特型谱方面非常相似，它们具有几个结构特征。它们的VH和VL区域由相同的VH、VK和JH基因编码，显示出相对相似的V(D)J重排，仅通过少数氨基酸替换而有所不同。在由mAb KS13诱导产生的五种抗 - id mAb中，mAb R1 - 38和R18 - 9利用了与抗 - id mAb KO3 - 34、K03 - 256和K03 - 335不同的多种遗传元件。这些结果表明，不同的V区组合可以在分析的抗原系统中赋予抗 - id特异性。mAb K03 - 34、K03 - 256和K03 - 335源自同一个B细胞克隆，因为它们使用相同的V、D和J基因，并具有相同的V(D)J重排。后三种抗 - id mAb仅因点突变而不同，这些点突变对三种抗 - id mAb的HLA - DQ3抗原模拟特性有显著影响。mAb K03 - 34是唯一一种在同基因和异种宿主中均能诱导抗HLA - DQ3抗体的抗体。抗 - id mAb K03 - 34的抗原模拟特性取决于其三维构象，因为在其VH和VL区域与HLA - DQ3抗原的α1和β1结构域之间未发现明显的氨基酸序列同源性。
