title: Human Langerhans cells capture measles virus through Langerin and present viral antigens to CD4⁺ T cells but are incapable of cross-presentation.
abstract: Langerhans cells (LCs) are a subset of DCs that reside in the upper respiratory tract and are ideally suited to sense respiratory virus infections. Measles virus (MV) is a highly infectious lymphotropic and myelotropic virus that enters the host via the respiratory tract. Here, we show that human primary LCs are capable of capturing MV through the C-type lectin Langerin. Both immature and mature LCs presented MV-derived antigens in the context of HLA class II to MV-specific CD4(+)  T cells. Immature LCs were not susceptible to productive infection by MV and did not present endogenous viral antigens in the context of HLA class I. In contrast, mature LCs could be infected by MV and presented de novo synthesized viral antigens to MV-specific CD8(+)  T cells. Notably, neither immature nor mature LCs were able to cross-present exogenous UV-inactivated MV or MV-infected apoptotic cells. The lack of direct infection of immature LCs, and the inability of both immature and mature LCs to cross-present MV antigens, suggest that human LCs may not be directly involved in priming MV-specific CD8(+)  T cells. Immune activation of LCs seems a prerequisite for MV infection of LCs and subsequent CD8(+)  T-cell priming via the endogenous antigen presentation pathway.
authors: Center of Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: Michiel
authors: M
authors: van der Vlist
authors: Lot
authors: L
authors: de Witte
authors: Rory D
authors: RD
authors: de Vries
authors: Manja
authors: M
authors: Litjens
authors: Marein A W P
authors: MA
authors: de Jong
authors: Donna
authors: D
authors: Fluitsma
authors: Rik L
authors: RL
authors: de Swart
authors: Teunis B H
authors: TB
authors: Geijtenbeek
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D002460:Cell Line; D045142:Cross-Priming / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008457:Measles / Q000276:immunology* / Q000821:virology; D008459:Measles virus / Q000276:immunology* / Q000472:pathogenicity; D051379:Mice; D011991:Receptors, Virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012137:Respiratory System / Q000473:pathology; D019076:Transgenes / Q000235:genetics
chemical_list: D015703:Antigens, CD; D000956:Antigens, Viral; C121916:CD207 protein, human; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D011991:Receptors, Virus