The immunogenicity of soluble haptenated polymers is determined by molecular mass and hapten valence.
The immunogenicity of soluble haptenated polymers is determined by molecular mass and hapten valence.
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DOI：
10.4049/jimmunol.143.4.1239
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发表时间：
1989-08
影响因子：
4.4
通讯作者：
R. Dintzis;M. Okajima;M. Middleton;G. Greene;H. Dintzis
中科院分区：
文献类型：
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作者：
R. Dintzis;M. Okajima;M. Middleton;G. Greene;H. Dintzis
据信，在相对缺乏 Ag 加工和 T 细胞帮助的情况下，T 细胞非依赖性 Ag 可以刺激抗体形成。先前对 2 型 T 细胞非依赖性 (TI-2) Ag DNP-聚丙烯酰胺的研究表明，当系统地改变分子质量和半抗原价时，此类分子的免疫原性潜力取决于可定义的分子特征。结果发现，要具有免疫原性，这些分子必须超过 100,000 Da 的阈值分子量和 20 的阈值半抗原价。本研究的目的是确定这些发现是否可以推广到属于 TI-2 类 Ag 的其他分子。系统地改变了五种化学性质不同的荧光素 (FL) 聚合物的分子特征，并测量了它们刺激 IgM 抗半抗原免疫反应的能力。用作载体的聚合物经过仔细的尺寸分级，由一种天然聚合物（葡聚糖）、一种改性天然聚合物（羧甲基纤维素）和三种合成聚合物（Ficoll、聚乙烯醇和聚丙烯酰胺）组成。载体的物理结构各不相同，从高度交联的聚蔗糖到稍微支化的葡聚糖，再到线性聚丙烯酰胺、羧甲基纤维素和聚乙烯醇。聚合物用 FL 进行半抗原化并进行尺寸分级，从而产生一组具有不同分子量、半抗原化合价和半抗原密度的分子。在腹膜内注射后体内测量对这些半抗原化聚合物的抗-FL IgM反应。将 FL 聚合物注射到盐水中，并在与未分级小鼠的未分级脾细胞培养后进行体外测量。与之前对 DNP-聚丙烯酰胺的研究一致，发现为了具有免疫原性，每种 FL-聚合物必须超过分子质量和半抗原价的可比阈值。当 FL 聚合物的质量和半抗原密度值位于可预测范围内时，就会出现最佳免疫原性。当这些最佳参数大幅增加或减少时，免疫原性就会降低。我们得出的结论是，可溶性半抗原聚合物的免疫原性取决于可预测的物理分子特征，并且相对独立于载体聚合物的化学组成和构象。
T cell-independent Ag are believed to stimulate antibody formation in the relative absence of Ag processing and T cell help. Previous studies on the type 2 T cell independent (TI-2) Ag DNP-polyacrylamide, have shown that when one systematically varies the molecular mass and hapten valence, the immunogenic potential of this type of molecule depends on definable molecular characteristics. It was found that to be immunogenic, these molecules had to exceed a threshold molecular mass of 100,000 Da and a threshold hapten valence of 20. The present study was undertaken to determine whether such findings could be generalized to other molecules belonging to the TI-2 class of Ag. The molecular characteristics of five chemically different fluoresceinated (FL)-polymers were systematically varied, and their ability to stimulate an IgM antihapten immune response was measured. The polymers used as carriers were carefully size-fractionated and consisted of one natural polymer (dextran), one modified natural polymer (carboxymethyl cellulose), and three synthetic polymers (Ficoll, polyvinyl alcohol, and polyacrylamide). The carriers varied in physical structure from the highly cross-linked Ficoll, to the somewhat branched dextran, to the linear polyacrylamide, carboxymethyl cellulose, and polyvinyl alcohol. Polymers were haptenated with FL and size-fractionated so as to yield a panel of molecules with varying molecular mass, hapten valence, and hapten density. Anti-FL IgM response to these haptenated polymers was measured in vivo after i.p. injection of the FL-polymer in saline, and measured in vitro after culture with unfractionated spleen cells from naive mice. In agreement with the previous studies on DNP-polyacrylamide, it was found that to be immunogenic, each of the FL-polymers had to exceed a comparable threshold value of molecular mass and of hapten valence. Optimal immunogenicity occurred when the FL-polymers had values of mass and hapten density lying within a predictable range. Immunogenicity decreased when these optimal parameters were substantially increased or decreased. We conclude that the immunogenicity of soluble haptenated polymers depends on predictable physical molecular characteristics, and is relatively independent of the chemical composition and conformation of the carrier polymer.