Characterization of HLA-DQalpha2/beta2, a new HLA class II molecule specifically expressed in human Langerhans cells
Characterization of HLA-DQalpha2/beta2, a new HLA class II molecule specifically expressed in human Langerhans cells.
Thèses de doctorat,
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Langerhans cells are the resident dendritic cells of the human epidermis, wherein they occupy a privileged position at the interface between the body and the external environment. To refine our knowledge on their specificities among the dendritic cells, a comparative analysis of their transcriptome was undertaken in the laboratory. In this way, the specific expression of the HLA-DQB2 gene by Langerhans cells was identified. HLA-DQA2/DQB2 genes are paralogous to the HLA-DQ-encoding HLA-DQA1/DQB1 genes, but have been described as remarkably lowly polymorphic for HLA class II genes and are strongly evolutionarily conserved. Up to date, their coordinated expression has never been reported. In this work, we confirm that HLA-DQA2 and HLA-DQB2 genes are specifically expressed in Langerhans cells. With the help of different transfected cell line models, we show that the HLA-DQα2 and HLA-DQβ2 chains associate together in the endoplasmic reticulum and, under the control of the chaperone invariant chain Ii, reach endosomal compartments. HLA-DQα2/β2 molecules interact with the endosomal chaperone HLA-DM and are expressed at the plasma membrane, where they mediate staphylococcal superantigen presentation to T cells. Taken together, those results suggest that HLA-DQα2/β2 molecules could represent a new type of lowly polymorphic HLA class II molecules specifically expressed in epidermal Langerhans cells.
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