CD1c bypasses lysosomes to present a lipopeptide antigen with 12 amino acids.
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.
Van Rhijn
Ildiko
I
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. i.vanrhijn@uu.nl
Young
David C
DC
De Jong
Annemieke
A
Vazquez
Jenny
J
Cheng
Tan-Yun
TY
Talekar
Rahul
R
Barral
Duarte C
DC
Barral
Duarte
D
León
Luis
L
Brenner
Michael B
MB
Katz
Joel T
JT
Riese
Richard
R
Ruprecht
Ruth M
RM
O'Connor
Peter B
PB
Costello
Catherine E
CE
Porcelli
Steven A
SA
Briken
Volker
V
Moody
D Branch
DB
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
D000596:Amino Acids; D000941:Antigens; D018949:Antigens, CD1; C437944:CD1C protein, human; D006023:Glycoproteins; D055666:Lipopeptides; D010080:Oxazoles; D011994:Recombinant Proteins; C585579:dideoxymycobactin