Villiers M B, Villiers C L, Laharie A M, Marche P N
Laboratoire Immunochimie, CEA-G, DBMS/ICH, INSERM U238, Université Joseph Fourier, Grenoble, France.
Immunopharmacology. 1999 May;42(1-3):151-7. doi: 10.1016/s0162-3109(99)00017-x.
Upon activation, complement C3 undergoes a conformational change and acquires the capacity to covalently bind to other proteins such as antigen and to interact with specific receptors; therefore, C3 is involved in cell mediated immune response. The adjuvant effect produced by linking C3-fragments to antigen has recently been described. We injected C3b-Ag complexes consisting of one molecule of C3b ester linked to one molecule of HEL to immunised mice, and we compared the C3b adjuvant activity with that of complete Freund's adjuvant. IgG titers elicited by HEL emulsified in CFA (HEL + CFA) were higher than those elicited by HEL-C3b, but decreased rapidly after a peak response around day 45 whereas HEL-C3b resulted in a continuous increase of anti-HEL response. Mice immunised with HEL + CFA then boosted with HEL-C3b gave significantly higher response than those boosted with HEL + CFA, indicating more efficient memory cell restimulation by C3b. HEL + CFA leads to better priming than HEL-C3b when mice are boosted with HEL-C3b. Thus, adjuvant effect of C3b is different from that of CFA, leading to more stable IgG production and better memory stimulation.
激活后,补体C3会发生构象变化,并获得与其他蛋白质(如抗原)共价结合以及与特定受体相互作用的能力;因此,C3参与细胞介导的免疫反应。最近已经描述了将C3片段与抗原连接所产生的佐剂效应。我们将由一分子C3b酯与一分子HEL连接而成的C3b-Ag复合物注射到免疫小鼠体内,并将C3b的佐剂活性与完全弗氏佐剂的佐剂活性进行比较。在CFA(HEL + CFA)中乳化的HEL引发的IgG滴度高于HEL-C3b引发的IgG滴度,但在第45天左右达到峰值反应后迅速下降,而HEL-C3b导致抗HEL反应持续增加。先用HEL + CFA免疫然后用HEL-C3b加强免疫的小鼠产生的反应明显高于用HEL + CFA加强免疫的小鼠,这表明C3b对记忆细胞的再刺激更有效。当用HEL-C3b对小鼠进行加强免疫时,HEL + CFA比HEL-C3b能产生更好的初次免疫。因此,C3b的佐剂效应与CFA不同,能导致更稳定的IgG产生和更好的记忆刺激。