Lopes L M, Hughson E, Anstee Q, O'Neil D, Katz D R, Chain B M
Department of Immunology, University College London Medical School, London, UK.
Immunology. 1999 Sep;98(1):16-26. doi: 10.1046/j.1365-2567.1999.00815.x.
This study explores the expression and the function of major histocompatibility complex class II in the intestinal epithelial cell line CaCo-2, which has been widely used as a model for the human gastrointestinal epithelium. Human leucocyte antigen (HLA)-DR expression on CaCo-2 cells is induceable by interferon-gamma (IFN-gamma), but responsiveness to IFN-gamma is dependent on cell differentiation and IFN-gamma availability at the basolateral cell surface. HLA-DR expression is concentrated in apical cytoplasmic vesicles and on the basolateral cell surface. Invariant chain is expressed in apical vesicles but is absent from the cell surface. Immunoprecipitation studies show a slow rate of dissociation of HLA-DR from Ii. Double labelling shows some overlap between HLA-DR expression and basolateral endosomal markers but no overlap with apical endosomal markers. Functional studies show processing and presentation of lysozyme endocytosed from the basolateral, but not apical surfaces. CaCo-2 cells may provide a useful model with which to dissect the antigen-processing pathways in polarized epithelial cells. The regulated access of antigens taken up from the gut lumen to the processing compartments may prevent overloading the immune system with antigens derived from normal gut contents.
本研究探讨主要组织相容性复合体II类分子在肠上皮细胞系CaCo-2中的表达及功能，该细胞系已被广泛用作人类胃肠道上皮的模型。CaCo-2细胞上的人类白细胞抗原（HLA）-DR表达可被γ干扰素（IFN-γ）诱导，但对IFN-γ的反应性取决于细胞分化以及基底外侧细胞表面的IFN-γ可用性。HLA-DR表达集中于顶端细胞质囊泡及基底外侧细胞表面。恒定链在顶端囊泡中表达，但在细胞表面不存在。免疫沉淀研究表明HLA-DR与Ii的解离速率较慢。双重标记显示HLA-DR表达与基底外侧内体标记物有部分重叠，但与顶端内体标记物无重叠。功能研究表明，从基底外侧而非顶端表面内吞的溶菌酶可被加工和呈递。CaCo-2细胞可能为剖析极化上皮细胞中的抗原加工途径提供一个有用的模型。从肠腔摄取的抗原对加工区室的调控性进入可能会防止源自正常肠内容物的抗原使免疫系统负担过重。
