title: Human leukocyte Antigen-DM polymorphisms in autoimmune diseases.
abstract: Classical MHC class II (MHCII) proteins present peptides for CD4(+) T-cell surveillance and are by far the most prominent risk factor for a number of autoimmune disorders. To date, many studies have shown that this link between particular MHCII alleles and disease depends on the MHCII's particular ability to bind and present certain peptides in specific physiological contexts. However, less attention has been paid to the non-classical MHCII molecule human leucocyte antigen-DM, which catalyses peptide exchange on classical MHCII proteins acting as a peptide editor. DM function impacts the presentation of both antigenic peptides in the periphery and key self-peptides during T-cell development in the thymus. In this way, DM activity directly influences the response to pathogens, as well as mechanisms of self-tolerance acquisition. While decreased DM editing of particular MHCII proteins has been proposed to be related to autoimmune disorders, no experimental evidence for different DM catalytic properties had been reported until recently. Biochemical and structural investigations, together with new animal models of loss of DM activity, have provided an attractive foundation for identifying different catalytic efficiencies for DM allotypes. Here, we revisit the current knowledge of DM function and discuss how DM function may impart autoimmunity at the organism level.
authors.affiliation: Protein Biochemistry Group, Institute for Chemistry and Biochemistry, Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, Berlin, Germany malvaro@zedat.fu-berlin.de.
authors.forename: Miguel
authors.identifier: 0000-0002-6019-3567
authors.initials: M
authors.lastname: Alvaro-Benito
authors.affiliation: Protein Biochemistry Group, Institute for Chemistry and Biochemistry, Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, Berlin, Germany.
authors.forename: Eliot
authors.initials: E
authors.lastname: Morrison
authors.affiliation: Protein Biochemistry Group, Institute for Chemistry and Biochemistry, Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, Berlin, Germany.
authors.forename: Marek
authors.initials: M
authors.lastname: Wieczorek
authors.affiliation: Protein Biochemistry Group, Institute for Chemistry and Biochemistry, Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, Berlin, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Sticht
authors.affiliation: Protein Biochemistry Group, Institute for Chemistry and Biochemistry, Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, Berlin, Germany chfreund@zedat.fu-berlin.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Freund
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D001327:Autoimmune Diseases / Q000235:genetics*; D000072669:Gene Editing; D020022:Genetic Predisposition to Disease; D006681:HLA-D Antigens / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide
chemical_list: D006681:HLA-D Antigens; C084245:HLA-DM antigens
keywords: antigen presentation; autoimmunity; human leucocyte antigen-DM; major histocompatibility complex of class II; peptidome; polymorphism