Distinct editing functions of natural HLA-DM allotypes impact antigen presentation and CD4^(+) T cell activation  

作　　者：Miguel Álvaro-Benito Eliot Morrison Friederike Ebner Esam T.Abualrous Marie Urbicht Marek Wieczorek Christian Freund 

机构地区：[1]Laboratory of Protein Biochemistry,Department of Biology,Chemistry and Pharmacy,Freie Universität Berlin,Thielallee 63,14195 Berlin,Germany [2]Institut für Immunologie,Department of Veterinary Medicine,Freie Universität Berlin,Robert-von-Ostertag-Str.7-13,14163 Berlin,Germany [3]Computational Molecular Biology Group,Institute for Mathematics,Freie Universität Berlin,Berlin,Germany

出　　处：《Cellular & Molecular Immunology》2020年第2期133-142,共10页中国免疫学杂志（英文版）

基　　金：supported by the Deutsche Forschungsgemeinschaft(DFG);C.F.is thankful for funding by the DFG(FR-1325/17–1,SFB958(project Z03);TRR186(projects A05,A11));M.A.-B.is thankful for funding from the Freie Universität Berlin Forschungskommision.

摘　　要：Classical human leukocyte antigen(HLA)molecules of the major histocompatibility classⅡ(MHCⅡ)complex present peptides for the development,surveillance and activation of CD4^(+) T cells.The nonclassical MHCⅡ-like protein HLA-DM(DM)catalyzes the exchange and loading of peptides onto MHCⅡmolecules,thereby shaping MHCⅡimmunopeptidomes.Natural variations of DM in both chains of the protein(DMA and DMB)have been hypothesized to impact peptide presentation,but no evidence for altered function has been reported.Here we define the presence of DM allotypes in human populations covered by the 1000 Genomes Project and probe their activity.The functional properties of several allotypes are investigated and show strong enhancement of peptide-induced T cell activation for a particular combination of DMA and DMB.Biochemical evidence suggests a broader pH activity profile for the new variant relative to that of the most commonly expressed DM allotype.Immunopeptidome analysis indicates that the compartmental activity of the new DM heterodimer extends beyond the late endosome and suggests that the natural variation of DM has profound effects on adaptive immunity when antigens bypass the canonical processing pathway.

关 键 词：MHC classⅡ Limited polymorphism HLA-DM Peptide editing Epitope selection Immunopeptidome 

分 类 号：R392[医药卫生—免疫学]