title: HLA-DQA2 and HLA-DQB2 genes are specifically expressed in human Langerhans cells and encode a new HLA class II molecule.
abstract: The precise role of human epidermal Langerhans cells (LCs) in immune response is highly controversial. While studying the gene expression profile of these cells, we were intrigued to identify the HLA-DQB2 gene as potentially expressed in LCs. Despite a strong evolutionary conservation of their sequences, the concomitant expression of the poorly polymorphic HLA-DQA2/HLA-DQB2 genes, paralogous to the HLA-DQA1/HLA-DQB1 genes, has never been detected in any cell type. We confirmed by RT-PCR that the HLA-DQA2 and -DQB2 genes are both expressed in LCs, but not in monocyte-derived dendritic cells, or in blood CD1c(+) or plasmacytoid dendritic cells. The presence of the HLA-DQβ2 chain in LCs could be demonstrated by Western blotting, whereas immunofluorescence revealed its localization in early endosomes. As in the case of other HLA class II molecules, the HLA-DQα2 and -DQβ2 chains formed heterodimers that had to associate with the invariant chain to reach endosomal compartments. HLA-DQα2/β2 heterodimers were expressed at the cell surface, where they could mediate staphylococcal superantigen stimulation of T cells. Interestingly, HLA-DQα2 and HLA-DQβ1 chains formed mixed heterodimers which efficiently left the endoplasmic reticulum. These observations strongly suggest that the poorly polymorphic HLA-DQA2 and -DQB2 genes should be considered to be of immunological importance. The HLA-DQα2/β2 molecules could influence the complexity of the repertoire of Ags presented by LCs.
authors.affiliation: INSERM, Unité Mixte de Recherche S725, Biologie des Cellules Dendritiques Humaines, Strasbourg, 67065 France.
authors.forename: Cedric
authors.initials: C
authors.lastname: Lenormand
authors.forename: Huguette
authors.initials: H
authors.lastname: Bausinger
authors.forename: Florence
authors.initials: F
authors.lastname: Gross
authors.forename: Francois
authors.initials: F
authors.lastname: Signorino-Gelo
authors.forename: Susanne
authors.initials: S
authors.lastname: Koch
authors.forename: Maryse
authors.initials: M
authors.lastname: Peressin
authors.forename: Dominique
authors.initials: D
authors.lastname: Fricker
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cazenave
authors.forename: Thomas
authors.initials: T
authors.lastname: Bieber
authors.forename: Daniel
authors.initials: D
authors.lastname: Hanau
authors.forename: Henri
authors.initials: H
authors.lastname: de la Salle
authors.forename: Sylvie
authors.initials: S
authors.lastname: Tourne
mesh_terms: D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000276:immunology; D015153:Blotting, Western; D002460:Cell Line; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000276:immunology; D011992:Endosomes / Q000235:genetics / Q000276:immunology; D005091:Exons; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D006801:Humans; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D010957:Plasmids; D055503:Protein Multimerization; D017422:Sequence Analysis, DNA
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D006683:HLA-DQ Antigens; C103596:HLA-DQA2 antigen; C040626:HLA-Dx antigen; D000949:Histocompatibility Antigens Class II; C045084:invariant chain