The Forgotten: Identification and Functional Characterization of MHC Class II Molecules H2-Eb2 and RT1-Db2

作者：Elisa Monzón‐Casanova, Ronald Rudolf, Lisa Starick, Ingrid Müller, Christian Söllner, Nora Müller, Nico Westphal, Tohru Miyoshi‐Akiyama, Takehiko Uchiyama, Ingolf Berberich, Lutz Walter, Thomas Herrmann · 发表于：The Journal of Immunology · 年份：2016 · DOI：10.4049/jimmunol.1403070 · 被引用次数：17 · 研究领域：Immune Cell Function and Interaction、Monoclonal and Polyclonal Antibodies Research、Immunotherapy and Immune Responses

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.