Antigenpresenting cell function

Tissue location, dendritic morphology, cell surface phenotype, and ability to migrate to T cell-rich areas make Langerhans cells ideally suited as antigen-presenting cells. Figure 3 outlines the generally accepted model for Langerhans cell-mediated T cell activation. Facilitated by the prominent cell surface dendritic processes, Langerhans cells take up protein antigens or protein—hapten complexes within epidermis. They then traverse the epidermal basement membrane and present MHC-restricted peptides to CD4+ or CD8+ T cells; antigen presentation occurs either within dermis, to memory T cells that have circulated in dermal capillaries, or within the paracortex area of regional lymph nodes, to naive T cells following Langerhans cells emigration through afferent lymphatics. Evidence to support this model has come from both in vitro and in vivo studies, and in both human and murine systems. Allergic contact dermatitis (e.g. poison ivy dermatitis) is the prototype clinical disease associated with sensitization to a contact allergen, Langerhans cell antigen presentation and T cell activation as outlined here.

Not surprisingly, freshly isolated Langerhans cells (analogous to Langerhans cells in situ), when compared to cultured Langerhans cells (analogous to Langerhans cells that have emigrated to regional lymph node), are more efficient at antigen uptake in vitro. Conversely, stimulation of naive T cells, a process that normally occurs within lymph nodes in vivo, is best performed by cultured Langerhans cells in vitro. The cell surface antigens present on freshly isolated and cultured Langerhans cells, as outlined in Table 3, are consistent with this functional data. For example, the high levels of cell surface MHC- and costimulatory molecules present on cultured Langerhans cells are critical for efficient stimulation of naive T cells. Additionally, Birbeck granules, which arc structures that may be involved in antigen uptake, are detected only in freshly isolated Langerhans cells.

U_| Antigen

U_| Antigen

Figure 3 Schematic diagram showing the function of Langerhans cells in mediating antigen-specific T cell activation. Following contact with an antigen or hapten (which becomes antigenic following binding to a protein carrier) on the skin surface (A), epidermal Langerhans cells take up and process antigen within MHC class I or class II compartments (B). Activated Langerhans cells, i.e. Langerhans cells exposed to antigen, migrate from epidermis and display antigenic peptides on their cell surface (C). For primary immune responses, activated Langerhans cells enter afferent lymphatics within skin and travel to regional lymph nodes (D). To facilitate activation of naive T cells, cell surface MHC and costimulatory molecules are upregulated during this migration. Within the paracortex of lymph node, stimulation of naive T cells occurs In an MHC-restricted antigen-specific manner (E). For secondary immune responses, activated Langerhans cells present antigen and stimulate memory T cells, which circulate in capillaries, within the dermis (F).

Figure 3 Schematic diagram showing the function of Langerhans cells in mediating antigen-specific T cell activation. Following contact with an antigen or hapten (which becomes antigenic following binding to a protein carrier) on the skin surface (A), epidermal Langerhans cells take up and process antigen within MHC class I or class II compartments (B). Activated Langerhans cells, i.e. Langerhans cells exposed to antigen, migrate from epidermis and display antigenic peptides on their cell surface (C). For primary immune responses, activated Langerhans cells enter afferent lymphatics within skin and travel to regional lymph nodes (D). To facilitate activation of naive T cells, cell surface MHC and costimulatory molecules are upregulated during this migration. Within the paracortex of lymph node, stimulation of naive T cells occurs In an MHC-restricted antigen-specific manner (E). For secondary immune responses, activated Langerhans cells present antigen and stimulate memory T cells, which circulate in capillaries, within the dermis (F).

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