CD1c bypasses lysosomes to present a lipopeptide antigen with 12 amino acids

Ildiko Van Rhijn, David C. Young, Annemieke De Jong, Jenny Vazquez, Tan Yun Cheng, Rahul Talekar, Duarte Barral, Luis León, Michael B. Brenner, Joel T. Katz, Richard Riese, Ruth M. Ruprecht, Peter B. O'Connor, Catherine E. Costello, Steven A. Porcelli, Volker Briken, D. Branch Moody

Research output: Contribution to journalArticle

39 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1409-1422
Number of pages14
JournalJournal of Experimental Medicine
Volume206
Issue number6
DOIs
StatePublished - Jun 8 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Van Rhijn, I., Young, D. C., De Jong, A., Vazquez, J., Cheng, T. Y., Talekar, R., Barral, D., León, L., Brenner, M. B., Katz, J. T., Riese, R., Ruprecht, R. M., O'Connor, P. B., Costello, C. E., Porcelli, S. A., Briken, V., & Moody, D. B. (2009). CD1c bypasses lysosomes to present a lipopeptide antigen with 12 amino acids. Journal of Experimental Medicine, 206(6), 1409-1422. https://doi.org/10.1084/jem.20082480