THE PROCESSING AND PRESENTATION OF MYCOBACTERIAL ANTIGENS BY HUMAN-MONOCYTES

THE PROCESSING AND PRESENTATION OF MYCOBACTERIAL ANTIGENS BY HUMAN-MONOCYTES
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DOI:
10.1002/eji.1830180506
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发表时间:
1988-05-01
影响因子:
5.4
通讯作者:
COLSTON, MJ
COLSTON, MJ
中科院分区:
医学3区
文献类型:
--
作者:
BHARDWAJ, V;COLSTON, MJ

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全照射结核分枝杆菌(Mtb.Gamma.)并对卡介苗(BCG)免疫者外周血单核细胞纯化蛋白衍生物(PPD)进行了研究。为了研究处理和呈现不同于T细胞识别和增殖的事件,单核细胞在不同的时间间隔内被抗原冲击并固定。递呈动力学研究表明,PPD的有效递呈需要2小时,Mtb-γ的递呈需要2-4小时,而激活T细胞的能力随着脉冲出现的时间间隔的增加而下降,因此反应在8-10小时内消失。以及PPD对T细胞的影响,表明加工是必不可少的。溶酶体促进剂氯喹、莫能菌素和亮肽素抑制这些抗原的提呈,提示溶酶体/内切体在加工过程中的作用。此外,单核细胞与最佳的抗原浓度孵育不同的时间长度,释放的决定因素仍然是抗原性的,但绕过了任何进一步处理的需要。加入未经处理或多聚甲醛固定在脉冲固定的细胞上的未启动的同基因单核细胞,即使在后来没有检测到反应的时间段,也能恢复反应。这种单核细胞与T细胞的第二次相互作用不是主要的组织相容性复合体,因为来自另一供者的单核细胞的加入是同样有效的。
The processing and presentation of whole irradiated Mycobacterium tuberculosis (Mtb.gamma.) and its purified protein derivative (PPD) by the peripheral blood monocytes from healthy Bacillus Calmette Guerin (BCG)-vaccinated individuals was investigated. To study processing and presentation as events distinct from T cell recognition and proliferation, monocytes were pulsed with antigens for varying time intervals and fixed. The kinetics of presentation indicate that up to 2 h was required for effective presentation of PPD and 2-4 h for Mtb.gamma., and the the ability to activate T cells declined as the time interval for which pulsing occurred was increased, so that responses were abolished by 8-10 h. Prefixed monocytes could not present Mtb.gamma. and PPD to T cells indicating that processing was an essential requisite. Lysosomotropic agents chloroquine, monensin, and leupeptin inhibited the presentation of these antigens suggesting the role of lysosomes/endosomes in processing. Furthermore, monocytes incubated with optimal concentration of antigens for different lengths of time released determinants which were still antigenic but circumvented the need for any further processing. Addition of nonprimed syngeneic monocytes, both untreated or paraformaldehyde fixed to cells which had been pulsed and fixed, restored the responses even at the later time periods when responses were not detected. This second interaction of the monocyte with T cells was not major histocompatibility complex restricted in that the addition of monocytes from another donor was equally effective.