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¹ Division of Rheumatology, Immunology and Allergy, ² Division of Infectious Disease, and ³ Division of Pulmonary Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115
⁴ Mass Spectrometry Resource, Boston University School of Medicine, Boston, MA 02118
⁵ Department of Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115
⁶ Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461
⁷ Department of Cell Biology and Molecular Genetics and Maryland Pathogen Research Institute, University of Maryland, College Park, MD 20742

CORRESPONDENCE D. Branch Moody: bmoody{at}rics.bwh.harvard.edu OR Ildiko Van Rhijn: i.vanrhijn{at}uu.nl

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.

Abbreviations used: AP, adaptor protein; DDM, dideoxymycobactin; ESI, electrospray ionization; FTICR, Fourier transform ion cyclotron resonance; GMM, glucose monomycolate; LAMP1, lysosome association membrane protein 1; m/z, mass-to-charge; MFI, mean fluorescence intensity; MPM, mannosyl phosphomycoketide; MS, mass spectrometry; QIT, quadrupole ion trapping.

© 2009 Van Rhijn et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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