Basic studies on adaptation the immune therapy to the patients with periodontal diseases by using synthetic peptides as an immunogen

作为第一个试验，以适应牙周病患者的免疫治疗，我们估计如何Ag 53被宿主免疫细胞识别，并获得随后的效应功能。我们确定了EOP患者Ag 53的主要T细胞表位，并从HLA-II类分子限制的角度对其进行了估计。本研究的结果如下。(1)We使用基于Ag 53氨基酸序列的重叠肽，从22名受试者（包括6名EOP患者和16名健康供体）建立了Ag 53特异性短期T细胞系。结果发现，活动期EOP患者的T细胞株均能识别Ag 53上的共同区（p141-p181），而健康人的T细胞株则表现出异质性特异性。（2）抗DRBL单克隆抗体可抑制Ag 53诱导的大多数T细胞株的增殖。(3)A从所有建立的Th细胞系产生大量IFN-γ。其它细胞因子IL-4、IL-5、IL-6和IL-10的产生在Th细胞系之间是不同的。（4）评价Th细胞产生的精氨酸谱对B细胞产生IgG的影响。产生大量Th 2型细胞因子对抗Th 1型细胞因子的Th细胞系诱导高IgG产生。但Th细胞系产生低的Th 2细胞因子对抗Th 1细胞因子。不诱导IgG产生。(5)A在产生IgG的培养物中检测到更大量的来自Th细胞的IL-5。这些结果表明，活动性EOP患者的141 - 181位AA残基可能包括Ag 53上的主要T细胞表位，而健康个体或非活动性EOP患者则不包括。为牙周病牙龈卟啉单胞菌感染的免疫治疗奠定基础

As the first trial to adapt the immune therapy to the patients with periodontal diseases, we estimated how Ag53 is recognized by host immune cells and derive subsequent effector functions. We determined major T cell epitopes of Ag53 in EOP patients, and estimated them from the viewpoint of the restriction of HLA class II molecules. The results of this study are as follows.(1)We established Ag53 specific short-termed T cell lines from 22 subjects including 6 EOP patients and 16 healthy donors, using overlapping peptides based on Ag53 amino acid sequences. We found that all T cell lines from active EOP patients recognized common region (pl4l-p18l) on Ag53, while those of healthy donors showed heterogeneous specificity(2)Anti-DRBL monoclonal antibody inhibited Ag53-induced proliferation of most of the T cell lines.(3)A large amount of IFN-gamma was produced from all of established Th cell lines. The other cytokine production, including IL-4, 5, 6 and 10, were different among the Th cell lines.(4)The effect of the cytokine-profile produced from Th cells on the lgG production from B cells was evaluated. The Th cell lines producing high amount of Th2 type cytokines against Thl cytokines induced high IgG production. But the Th cell lines, which produced low Th2 cytokines against Thl cytokines. Did not induce the IgG production.(5)A larger amount of IL-5 from Th cells was detected in the culture with IgG production. compared to the culture without IgG production.These results suggest that AA residues from 14 1 to 181 is supposed to include major T cell epitope on Ag53 for active EOP patients but not for healthy individuals or inactive EOP patients. which might be interested in the establishment of the immune therapy for P gingivalisx infection in periodontal diseases