Intestinal epithelial cells use two distinct pathways for HLA class II antigen processing
Intestinal epithelial cells use two distinct pathways for HLA class II antigen processing
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DOI：
10.1172/jci119514
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发表时间：
1997-07-01
影响因子：
15.9
通讯作者：
Nepom, GT
中科院分区：
文献类型：
--
作者：
Hershberg, RM;Framson, PE;Nepom, GT
肠上皮细胞组成性地表达低水平的HLA II类分子，在粘膜炎症包括炎症性肠病的情况下表达水平升高。通过对HLA II类抗原加工途径的分子分析，研究了肠上皮细胞作为α - β CD4(+) T淋巴细胞的抗原提呈细胞的能力。我们已经证明肠上皮细胞含有丰富的组织蛋白酶组成水平，被证明在HLA II类介导的抗原呈递中起作用。利用HLA-DR限制性T细胞和逆转录病毒介导的HLA-DR等位基因转移到肠上皮细胞系HT-29和T84中，通过γ - ifn激活这些细胞，诱导了不变链和HLA-DM α β的表达，从而促进了紧凑的、sds稳定的HLA-DR α β异源二聚体的形成。我们证明了在促炎细胞存在的情况下，有效的抗原加工和呈递到CD4(+) T淋巴细胞。γ - ifn存在下的II类加工途径和递呈与传统抗原递呈细胞观察到的没有区别。在没有γ - ifn的情况下，肠上皮细胞也会发生抗原加工，与γ - lfn刺激后的情况相反，抗原加工需要高浓度的抗原，并且不受蛋白酶抑制剂胰肽的抑制。这些数据表明，在存在或不存在粘膜炎症的情况下，在具有不同免疫调节特性的肠细胞中使用两种不同的HLA II类抗原加工途径。
Intestinal epithelial cells express a low level of HLA class II molecules constitutively, with elevated levels seen in the setting of mucosal inflammation including inflammatory bowel disease, The ability of intestinal epithelial cells to act as antigen presenting cells for alpha beta CD4(+) T lymphocytes was examined through a molecular analysis of the HLA class II antigen processing pathway. We have shown that intestinal epithelial cells contain abundant constitutive levels of the cathepsin proteases proven to function in HLA class II mediated antigen presentation. Activation of these cells by gamma-IFN induced the expression of invariant chain and HLA-DM alpha beta, thus facilitating the formation of compact, SDS-stable HLA-DR alpha beta heterodimers, Using HLA-DR-restricted T cells and retroviral mediated gene transfer of HLA-DR alleles into the intestinal epithelial cell lines HT-29 and T84. we demonstrated efficient antigen processing and presentation to CD4(+) T lymphocytes in the presence of the proinflammatory. cytokine gamma-IFN, The class II processing pathway and presentation in the presence of gamma-IFN was indistinguishable from that observed with a conventional antigen presenting cell. Antigen processing also occurred in intestinal epithelial cells in the absence of gamma-IFN, and in contrast to that seen after stimulation with gamma-LFN, required high concentration of antigen and was not inhibited by the protease inhibitor leupeptin. These data suggest the use of two distinct pathways of HLA class II antigen processing in enterocytes with differential immunomodulatory properties in the presence or absence of mucosal inflammation.