title: CD1c bypasses lysosomes to present a lipopeptide antigen with 12 amino acids.
abstract: The recent discovery of dideoxymycobactin (DDM) as a ligand for CD1a demonstrates how a nonribosomal lipopeptide antigen is presented to T cells. DDM contains an unusual acylation motif and a peptide sequence present only in mycobacteria, but its discovery raises the possibility that ribosomally produced viral or mammalian proteins that commonly undergo lipidation might also function as antigens. To test this, we measured T cell responses to synthetic acylpeptides that mimic lipoproteins produced by cells and viruses. CD1c presented an N-acyl glycine dodecamer peptide (lipo-12) to human T cells, and the response was specific for the acyl linkage as well as the peptide length and sequence. Thus, CD1c represents the second member of the CD1 family to present lipopeptides. lipo-12 was efficiently recognized when presented by intact cells, and unlike DDM, it was inactivated by proteases and augmented by protease inhibitors. Although lysosomes often promote antigen presentation by CD1, rerouting CD1c to lysosomes by mutating CD1 tail sequences caused reduction in lipo-12 presentation. Thus, although certain antigens require antigen processing in lysosomes, others are destroyed there, providing a hypothesis for the evolutionary conservation of large CD1 families containing isoforms that survey early endosomal pathways.
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. i.vanrhijn@uu.nl
authors.forename: Ildiko
authors.initials: I
authors.lastname: Van Rhijn
authors.forename: David C
authors.initials: DC
authors.lastname: Young
authors.forename: Annemieke
authors.initials: A
authors.lastname: De Jong
authors.forename: Jenny
authors.initials: J
authors.lastname: Vazquez
authors.forename: Tan-Yun
authors.initials: TY
authors.lastname: Cheng
authors.forename: Rahul
authors.initials: R
authors.lastname: Talekar
authors.forename: Duarte C
authors.initials: DC
authors.lastname: Barral
authors.forename: Duarte
authors.initials: D
authors.lastname: Barral
authors.forename: Luis
authors.initials: L
authors.lastname: León
authors.forename: Michael B
authors.initials: MB
authors.lastname: Brenner
authors.forename: Joel T
authors.initials: JT
authors.lastname: Katz
authors.forename: Richard
authors.initials: R
authors.lastname: Riese
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Ruprecht
authors.forename: Peter B
authors.initials: PB
authors.lastname: O'Connor
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Costello
authors.forename: Steven A
authors.initials: SA
authors.lastname: Porcelli
authors.forename: Volker
authors.initials: V
authors.lastname: Briken
authors.forename: D Branch
authors.initials: DB
authors.lastname: Moody
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids; D000818:Animals; D000941:Antigens / Q000235:genetics / Q000276:immunology; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D055666:Lipopeptides / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D008247:Lysosomes / Q000378:metabolism*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010080:Oxazoles / Q000737:chemistry / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000596:Amino Acids; D000941:Antigens; D018949:Antigens, CD1; C437944:CD1C protein, human; D006023:Glycoproteins; D055666:Lipopeptides; D010080:Oxazoles; D011994:Recombinant Proteins; C585579:dideoxymycobactin