Becker D, Neiss U, Neis S, Reske K, Knop J
Department of Dermatology, University of Mainz, Germany.
J Invest Dermatol. 1992 May;98(5):700-5. doi: 10.1111/1523-1747.ep12499912.
MHC class II molecules play an important role during the sensitization phase of allergic contact dermatitis. To study the influence of contact allergens on the expression of these molecules by murine epidermal Langerhans cells (LC), we performed a flow-cytofluorometric analysis of the Ia-antigen expression after in vivo application of contact allergens. A distinct decrease in the Ia-antigen expression of the entire LC population was noticed 3 h after in vivo application of the contact allergen 2,4-dinitrofluorobenzene (DNFB). This decrease was transient and balanced 24 h after in vivo application of DNFB. A downregulation was also detectable after in vivo application of the contact allergens 1-chloro-2,4-dinitrobenzene (DNCB), oxazolone, K2Cr2O7, 2,4,6-trinitrochlorobenzene (TNCB), and toxic concentrations of the irritant compound sodium dodecyl sulfate (SDS). In vitro studies showed that freshly prepared as well as 3-d cultured LC downregulated their Ia-antigen expression in the presence of DNFB, which was used as a model compound. This decrease was not inhibited by the MHC class II molecule transport-inhibitor brefeldin A nor by the ionophore monensin. The inhibition of receptor-mediated endocytosis with hypertonic media (0.45 M sucrose) abolished the DNFB-mediated downregulation of Ia-antigen expression. An accelerated clearance of cell-surface-expressed antibody-labeled IA molecules was detectable in the presence of DNFB. Internalization studies carried out with peroxidase-labeled anti-IA-antibody complexes showed remarkable alterations in the intracellular distribution of endocytosed material under the influence of subtoxic concentrations of DNFB, DNCB, K2Cr2O7, and TNCB. The irritant substance sodium dodecyl sulfate (SDS) influenced the intracellular distribution pattern of internalized material only when used in toxic concentrations. An augmented participation of MHC class II molecules in endocytotic processes is mediated by reactive substances like contact allergens and might contribute to the processing and presentation of these compounds.
MHC II类分子在过敏性接触性皮炎的致敏阶段发挥重要作用。为了研究接触性变应原对小鼠表皮朗格汉斯细胞（LC）中这些分子表达的影响，我们在体内应用接触性变应原后，对Ia抗原表达进行了流式细胞荧光分析。在体内应用接触性变应原2,4-二硝基氟苯（DNFB）3小时后，整个LC群体的Ia抗原表达明显下降。这种下降是短暂的，在体内应用DNFB 24小时后达到平衡。在体内应用接触性变应原1-氯-2,4-二硝基苯（DNCB）、恶唑酮、重铬酸钾（K2Cr2O7）、2,4,6-三硝基氯苯（TNCB）以及刺激性化合物十二烷基硫酸钠（SDS）的毒性浓度后，也可检测到下调。体外研究表明，以DNFB作为模型化合物，新鲜制备的以及培养3天的LC在DNFB存在的情况下会下调其Ia抗原表达。这种下降不受MHC II类分子转运抑制剂布雷菲德菌素A或离子载体莫能菌素的抑制。用高渗介质（0.45M蔗糖）抑制受体介导的内吞作用可消除DNFB介导的Ia抗原表达下调。在DNFB存在的情况下，可检测到细胞表面表达的抗体标记的IA分子的清除加速。用过氧化物酶标记的抗IA抗体复合物进行的内化研究表明，在亚毒性浓度的DNFB、DNCB、K2Cr2O7和TNCB的影响下，内吞物质的细胞内分布发生了显著变化。刺激性物质十二烷基硫酸钠（SDS）仅在使用毒性浓度时才会影响内化物质的细胞内分布模式。接触性变应原等反应性物质介导MHC II类分子在胞吞过程中的参与增加，这可能有助于这些化合物的加工和呈递。
