Fong S, Chen P, Nitecki D E, Goodman J W
Mol Cell Biochem. 1979 Jun 15;25(3):131-42. doi: 10.1007/BF00235363.
As an approach to the elucidation of the essential steps in the immune pathway, the uptake and retention of immunogenic and non-immunogenic analogs of a monofunctional antigen by guinea pig macrophages and the efficiency of macrophages pulsed with the compounds to present antigen to sensitized T lymphocytes were compared. L-Tyrosine-azobenzene-p-arsonate (RAT) and its non-immunogenic analog, 4-hydroxyphenyl-n-propane-3-azobenzene-p-arsonate (RAN), react similarly with antiarsonate antibody, but RAN, unlike RAT, is unable to induce cellular immunity in guinea pigs. The uptake and retention patterns of the two compounds by macrophages differed in that, at a given time, more RAN than RAT was retained and detectable on cell surfaces by anti-arsonate antibody. Equivalent numbers of T lymphocytes from guinea pigs sensitized to RAT formed antigen-dependent clusters with macrophages pulsed with either RAT or RAN after 24 hr in culture, but not with macrophages pulsed with an azobenzenoid compound of unrelated specificity. On the other hand, T lymphocytes from guinea pigs immunized with RAN showed no significant capacity to bind to macrophages which had been pulsed with any of the compounds. The number of lymphocytes from RAT-sensitized animals which bound to RAT-pulsed macrophages remained relatively stable over a 48 hr period, whereas clusters of the same lymphocytes with RAN-pulsed macrophages dissocitated to background levels within that time. Early cluster formation mediated by RAN, as well as its ability to induce transient specific T cell unresponsiveness to RAT in vivo, indicate that T cells are capable of recognizing (binding) the non-immunogen. However, such early, and perhaps weak, interaction with RAN-pulsed macrophages did not induce DNA synthesis by T cells. Anti-Ia serum completely blocked cluster formation mediated by either RAT or RAN. Thus, the only significant distinction disclosed by these studies between the immunogenic and non-immunogenic compounds was the stability of macrophage-T cell interaction as determined by the persistence of antigen mediated cell clusters in culture, suggesting that this may be a factor in immunogenic discrimination.
为了阐明免疫途径中的关键步骤，比较了豚鼠巨噬细胞对单功能抗原的免疫原性和非免疫原性类似物的摄取和保留情况，以及用这些化合物脉冲处理的巨噬细胞将抗原呈递给致敏T淋巴细胞的效率。L-酪氨酸-偶氮苯-对-砷酸盐（RAT）及其非免疫原性类似物4-羟基苯基-n-丙烷-3-偶氮苯-对-砷酸盐（RAN）与抗砷酸盐抗体的反应相似，但与RAT不同，RAN不能在豚鼠中诱导细胞免疫。巨噬细胞对这两种化合物的摄取和保留模式有所不同，即在给定时间，抗砷酸盐抗体在细胞表面检测到的RAN保留量比RAT多。来自对RAT致敏的豚鼠的等量T淋巴细胞，在培养24小时后，与用RAT或RAN脉冲处理的巨噬细胞形成了抗原依赖性簇，但与用具有无关特异性的偶氮苯化合物脉冲处理的巨噬细胞没有形成簇。另一方面，用RAN免疫的豚鼠的T淋巴细胞，对用任何一种化合物脉冲处理的巨噬细胞没有明显的结合能力。来自RAT致敏动物的与RAT脉冲处理的巨噬细胞结合的淋巴细胞数量在48小时内保持相对稳定，而同一淋巴细胞与RAN脉冲处理的巨噬细胞形成的簇在这段时间内解离至背景水平。RAN介导的早期簇形成及其在体内诱导T细胞对RAT短暂特异性无反应的能力，表明T细胞能够识别（结合）非免疫原。然而，与RAN脉冲处理的巨噬细胞的这种早期且可能较弱的相互作用并没有诱导T细胞的DNA合成。抗Ia血清完全阻断了由RAT或RAN介导的簇形成。因此，这些研究揭示的免疫原性和非免疫原性化合物之间唯一显著的区别是，巨噬细胞与T细胞相互作用的稳定性，这是由培养中抗原介导的细胞簇的持续存在所决定的，这表明这可能是免疫原性区分的一个因素。
