title: The Forgotten: Identification and Functional Characterization of MHC Class II Molecules H2-Eb2 and RT1-Db2.
abstract: In this article, we report the complete coding sequence and to our knowledge, the first functional analysis of two homologous nonclassical MHC class II genes: RT1-Db2 of rat and H2-Eb2 of mouse. They differ in important aspects compared with the classical class II β1 molecules: their mRNA expression by APCs is much lower, they show minimal polymorphism in the Ag-binding domain, and they lack N-glycosylation and the highly conserved histidine 81. Also, their cytoplasmic region is completely different and longer. To study and compare them with their classical counterparts, we transduced them in different cell lines. These studies show that they can pair with the classical α-chains (RT1-Da and H2-Ea) and are expressed at the cell surface where they can present superantigens. Interestingly, compared with the classical molecules, they have an extraordinary capacity to present the superantigen Yersinia pseudotuberculosis mitogen. Taken together, our findings suggest that the b2 genes, together with the respective α-chain genes, encode for H2-E2 or RT1-D2 molecules, which could function as Ag-presenting molecules for a particular class of Ags, as modulators of Ag presentation like nonclassical nonpolymorphic class II molecules DM and DO do, or even as players outside the immune system.
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, 97078 Würzburg, Germany; herrmann-t@vim.uni-wuerzburg.de elisa.monzon-casanova@babraham.ac.uk.
authors.forename: Elisa
authors.initials: E
authors.lastname: Monzón-Casanova
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, 97078 Würzburg, Germany;
authors.forename: Ronald
authors.initials: R
authors.lastname: Rudolf
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, 97078 Würzburg, Germany;
authors.forename: Lisa
authors.initials: L
authors.lastname: Starick
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, 97078 Würzburg, Germany;
authors.forename: Ingrid
authors.initials: I
authors.lastname: Müller
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, 97078 Würzburg, Germany;
authors.forename: Christian
authors.initials: C
authors.lastname: Söllner
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, 97078 Würzburg, Germany;
authors.forename: Nora
authors.initials: N
authors.lastname: Müller
authors.affiliation: German Primate Center, Leibniz Institute of Primate Research, 37077 Göttingen, Germany; and.
authors.forename: Nico
authors.initials: N
authors.lastname: Westphal
authors.affiliation: Department of Microbiology and Immunology, Tokyo Women's Medical University, 162-8666 Tokyo, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Miyoshi-Akiyama
authors.affiliation: Department of Microbiology and Immunology, Tokyo Women's Medical University, 162-8666 Tokyo, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Uchiyama
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, 97078 Würzburg, Germany;
authors.forename: Ingolf
authors.initials: I
authors.lastname: Berberich
authors.affiliation: German Primate Center, Leibniz Institute of Primate Research, 37077 Göttingen, Germany; and.
authors.forename: Lutz
authors.identifier: http://orcid.org/0000-0001-9408-3131
authors.initials: L
authors.lastname: Walter
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, 97078 Würzburg, Germany; herrmann-t@vim.uni-wuerzburg.de elisa.monzon-casanova@babraham.ac.uk.
authors.forename: Thomas
authors.identifier: http://orcid.org/0000-0002-1093-0194
authors.initials: T
authors.lastname: Herrmann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D015153:Blotting, Western; D002469:Cell Separation; D005434:Flow Cytometry; D006649:Histocompatibility Antigens / Q000235:genetics* / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D014161:Transduction, Genetic
chemical_list: D006649:Histocompatibility Antigens; D000949:Histocompatibility Antigens Class II; C038353:histocompatibility antigens RT, rat