Processing of complex antigens and simple hapten-like molecules by epidermal Langerhans cells

Abstract

Langerhans cells (LCs) are antigen-presenting cells of the skin that trap small contact-sensitizing molecules and induce cutaneous hypersensitivity. LCs can present larger molecules but the mechanisms of processing have required investigation. A system combining in vitro culture of antigen with epidermal cells in the presence of inhibitors, followed by fixation and transfer of these antigen/drug-treated epidermal cells to naive mice, was developed to investigate the steps of antigen processing. Langerhans cells undertake similar, but not identical, pathways for the processing of simple and complex molecules. Complex molecules such as trinitrophenyl conjugated to ovalbumin (TNP-OVA) were internalized and modification required a chloroquine-sensitive proteolysis step and a cycloheximide-sensitive protein synthesis step. This modified product was actively recycled to the cell membrane as presentation was inhibited by blocking receptor translocation with either monensin or cytochalasin B. Small contact sensitizers such as trinitrophenyl did not undergo modification but required internalization and presentation was also inhibited by blocking receptor translocation.

Transdermal immunization with large proteins by means of ultradeformable drug carriers

“…Cultured Langerhans cells, on the contrary, do not process efficiently but can present pre-processed proteins to T cells extremely well [l]. In general, antigen fragments are presented differently from the large epitopes [14]. It has, therefore, been postulated that Langerhans cells trap antigens in the epidermis and carry them to the draining lymph nodes where the corresponding polypeptide fragments are finally presented to T cells [l].…”

Human epidermal Langerhans cells lack functional mannose receptors and a fully developed endosomal/lysosomal compartment for loading of HLA class II molecules

“…Efficient uptake of (protein) antigens, either through specific receptor-mediated endocytosis and/or (macro)pinocytosis might, therefore, be expected. Several studies have shown that freshly isolated murine LC endocytose protein antigens, and the high-affinity receptor for IgE (Fc 4 R1) has been implicated in the uptake of allergens by human epidermal LC [13,14,[27][28][29][30].…”

Evaluation of the Capacity of Dendritic Cells Derived from Cord Blood CD34+ Precursors to Present Haptens to Unsensitized Autologous T Cells In Vitro

“…These findings suggest that an active process, including perhaps internalization and processing, is required after TNP or FITC molecule binding. Internalization of membrane molecules has been shown after hapten treatment or hapten-carrier contact with murine Langerhans cells (Becker et al, 1995;Lempertz et al, 1996); however, if the need for processing is well established with hapten-carrier complexes (Ma et al, 1994;Woods et al, 1995), it remains controversial with hapten alone (Moulon et al, 1993).…”