Van Rhijn, I., Young, D. C., De Jong, Annemieke, Vazquez, Jenny, Cheng, Tan-Yun, Talekar, Rahul, Barral, D. C., Leon, L. (Luis), Brenner, M. B. (Michael B.), Katz, Joel T., Riese, R., Ruprecht, Ruth Margrit, 1947-, O'Connor, Peter B., Costello, Catherine E., Porcelli, Steven Anthony, Briken, V. and Moody, D. Branch. (2009) CD1c bypasses lysosomes to present a lipopeptide antigen with 12 amino acids. Journal of Experimental Medicine, Vol.206 (No.6). pp. 1409-1422. ISSN 0022-1007

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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.

Item Type:	Journal Article
Subjects:	Q Science > QD Chemistry Q Science > QP Physiology Q Science > QR Microbiology > QR180 Immunology
Divisions:	Faculty of Science > Chemistry
Library of Congress Subject Headings (LCSH):	CD antigens, T cells, Major histocompatibility complex, Lysosomes, Peptides, Acylation, Amino acids
Journal or Publication Title:	Journal of Experimental Medicine
Publisher:	Rockefeller University Press
ISSN:	0022-1007
Official Date:	8 June 2009
Volume:	Vol.206
Number:	No.6
Number of Pages:	14
Page Range:	pp. 1409-1422
Identification Number:	10.1084/jem.20082480
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	National Institute of Allergy and Infectious Diseases (U.S.) (NIAID), National Institute of Arthritis and Musculoskeletal and Skin Diseases (U.S.) (NIAMSD), American Lung Association (ALA), National Institutes of Health (U.S.) (NIH), Pew Scholars Program in the Biomedical Sciences, National Center for Research Resources (U.S.) (NCRR), Burroughs Wellcome Fund
Grant number:	R01 AI049313, AI45889 (NIAID), R01 AR048632 (NIAMSD), RT-95-N (ALA), P41 RR10888 (NCRR)
URI:	http://wrap.warwick.ac.uk/id/eprint/40608

Data sourced from Thomson Reuters' Web of Knowledge

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