title: CD1c presentation of synthetic glycolipid antigens with foreign alkyl branching motifs.
abstract: Human CD1c is a protein that activates alphabeta T cells by presenting self antigens, synthetic mannosyl phosphodolichols, and mycobacterial mannosyl phosphopolyketides. To determine which molecular features of antigen structure confer a T cell response, we measured activation by structurally divergent Mycobacterium tuberculosis mannosyl-beta1-phosphomycoketides and synthetic analogs with either stereorandom or stereospecific methyl branching patterns. T cell responses required both a phosphate and a beta-linked mannose unit, and they showed preference for C(30-34) lipid units with methyl branches in the S-configuration. Thus, T cell responses were strongest for synthetic compounds that mimicked the natural branched lipids produced by mycobacterial polyketide synthase 12. Incorporation of methylmalonate to form branched lipids is a common bacterial lipid-synthesis pathway that is absent in vertebrates. Therefore, the preferential recognition of branched lipids may represent a new lipid-based pathogen-associated molecular pattern.
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Smith Building Room 538, One Jimmy Fund Way, Boston, MA 02115, USA.
authors.forename: Annemieke
authors.initials: A
authors.lastname: de Jong
authors.forename: Eva Casas
authors.initials: EC
authors.lastname: Arce
authors.forename: Tan-Yun
authors.initials: TY
authors.lastname: Cheng
authors.forename: Ruben P
authors.initials: RP
authors.lastname: van Summeren
authors.forename: Ben L
authors.initials: BL
authors.lastname: Feringa
authors.forename: Vadim
authors.initials: V
authors.lastname: Dudkin
authors.forename: David
authors.initials: D
authors.lastname: Crich
authors.forename: Isamu
authors.initials: I
authors.lastname: Matsunaga
authors.forename: Adriaan J
authors.initials: AJ
authors.lastname: Minnaard
authors.forename: D Branch
authors.initials: DB
authors.lastname: Moody
mesh_terms: D000941:Antigens / Q000378:metabolism*; D018949:Antigens, CD1 / Q000378:metabolism*; D006017:Glycolipids / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000941:Antigens; D018949:Antigens, CD1; C437944:CD1C protein, human; D006017:Glycolipids; D006023:Glycoproteins