PROCESSING AND PRESENTATION OF INTACT HEN EGG-WHITE LYSOZYME BY DENDRITIC CELLS

PROCESSING AND PRESENTATION OF INTACT HEN EGG-WHITE LYSOZYME BY DENDRITIC CELLS
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DOI:
10.1002/eji.1830220925
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发表时间:
1992-09-01
影响因子:
5.4
通讯作者:
MELIEF, CJM
MELIEF, CJM
中科院分区:
医学3区
文献类型:
--
作者:
DEBRUIJN, MLH;NIELAND, JD;MELIEF, CJM

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淋巴组织中的树突状细胞作为高度特化的抗原呈递细胞对于诱导T淋巴细胞应答具有关键重要性。关于树突状细胞对完整蛋白质的抗原加工,已经发表了许多结果。我们现在报道,从H-2k小鼠脾脏分离的高度纯化的树突状细胞非常有效地产生完整的鸡蛋清溶菌酶(HEL)蛋白的免疫原性片段,以呈递给I-A(k)限制性T杂交瘤细胞系,其对HEL肽46-61具有特异性。树突状细胞需要的HEL蛋白比脂多糖诱导的B细胞胚少100倍才能有效呈递。观察树突状细胞摄取I-125标记的HEL蛋白和氯喹处理抑制HEL蛋白的呈递。这表明了一个内吞过程和酸化隔室的参与。由于与完整HEL蛋白孵育的树突状细胞的上清液含有免疫原性片段,因此获得了树突状细胞加工HEL蛋白的进一步证据。当HEL蛋白共价偶联到珠粒时,树突状细胞不能摄取这些珠粒,但仍然可以加工HEL蛋白用于呈递。这表明HEL蛋白的细胞表面加工,尽管不能排除从珠粒释放的HEL蛋白的内化。总之,这些数据表明H-2(k)树突状细胞能够加工和呈递完整的HEL蛋白。
Dendritic cells in lymphoid tissues are of key importance as highly specialized antigen-presenting cells for the induction of T lymphocyte responses. Conflicting results have been published regarding antigen processing of intact proteins by dendritic cells. We now report that highly purified dendritic cells isolated from H-2 k mouse spleens very efficiently generated immunogenic fragments of intact hen egg-white lysozyme (HEL) protein to present to an I-A(k)-restricted T hybridoma cell line, specific for HEL peptide 46-61. Dendritic cells required 100 times less HEL protein than lipopolysaccharide-induced B cell blasts for effective presentation. Uptake of I-125-labeled HEL protein by dendritic cells and inhibition of presentation of HEL protein by chloroquine treatment was observed. This indicates an endocytotic process and the involvement of acidified compartments. Since the supernatant of dendritic cells, that were incubated with intact HEL protein, contained immunogenic fragments, further evidence for processing of HEL protein by dendritic cells was obtained. When HEL protein was covalently coupled to beads, dendritic cells were not able to ingest these beads, but could still process HEL protein for presentation. This suggests cell surface processing of HEL protein, although internalization of HEL protein released from the beads cannot be excluded. Taken together, these data show that H-2(k) dendritic cells are capable of processing and presenting intact HEL protein.