Epidermal Langerhans cells efficiently mediate CD1a-dependent presentation of microbial lipid antigens to T cells

Langerhans cells are a critical component of skin immunity, capable of capturing protein antigens in the epidermis and presenting them to specific T cells in the context of major histocompatibility complex class II molecules. Recently, a major histocompatibility complex independent pathway of lipid antigen presentation has been identified and is mediated by molecules of the CD1 family (CD1a, CD1b, CD1c, and CD1d). Because Langerhans cells are professional antigen-presenting cells and express CD1a molecules prominently, we hypothesized that Langerhans cells might play a role in T cell responses directed against not only peptide antigens but also lipid antigens. Here, we show that freshly isolated immature Langerhans cells as well as mature Langerhans cells that have migrated from the epidermis are efficient in presenting foreign microbial lipid antigens to specific T cells whereas dermal dendritic cells express much less CD1a molecules and function inefficiently. Further, we found that Langerhans cells migrating from epidermal sheets that were exposed to microbial lipid antigens expressed lipid-antigen-loaded CD1a molecules on the cell surface, resulting in activation of specific T cells. These results underscore an outstanding ability of Langerhans cells to mediate CD1a-dependent lipid antigen presentation. Thus, Langerhans-cell-mediated skin immunity may involve T cell recognition of both peptide and lipid antigens.