Human Resident Langerhans Cells Display a Lysosomal compartment Enriched in MHC Class II

Langerhans cells are the antigen-presenting cells of the skin, belonging to the family of dendritic cells, which present exogenous antigens in the context of major histocompatibility complex class II (MHC-II) molecules to CD4+ T lymphocytes. Langerhans cells are potent stimulators of different T-cell responses including primary immune responses. Culturing of Langerhans cells leads to modulation of their phenotype and function, as they seem more capable of activating T cells, whereas freshly isolated Langerhans cells are specialized in the endocytosing and processing of antigen. We studied the intracellular distribution of MHC-II molecules and invariant chain (I-chain) in resident Langerhans cells using immunogold labeling of ultrathin cryosections of human epidermis and found the majority of intracellular MHC-II molecules present on membranes of rough endoplasmic reticulum and in so-called MHC-II-enriched compartments (MIIC). The MIIC appeared to be negative for the cation-independent mannose 6-phosphate receptor and positive for the lysosomal enzyme β-hexosaminidase and acquired the endocytotic tracer, cationized horseradish peroxidase, only after 60 min of internalization. Taken together, these data show that MIIC in Langerhans cells share characteristics with lysosomes. I-chain, which is associated with MHC-II molecules in early biosynthetic compartments, was found in the rough endoplasmic reticulum and Golgi complex, but was detected only occasionally in MIIC and at the plasma membrane. MIIC with internal membrane vesicles showed some I-chain labeling, suggesting that these are newly formed MIIC in which degradation of the I-chain is not yet complete