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

被引:44
作者
Van Rhijn, Ildiko [1 ]
Young, David C. [1 ]
De Jong, Annemieke [1 ]
Vazquez, Jenny [4 ]
Cheng, Tan-Yun [1 ]
Talekar, Rahul [1 ]
Barral, Duarte [1 ]
Leon, Luis [1 ]
Brenner, Michael B. [1 ]
Katz, Joel T. [2 ]
Riese, Richard [3 ]
Ruprecht, Ruth M. [5 ]
O'Connor, Peter B. [4 ]
Costello, Catherine E. [4 ]
Porcelli, Steven A. [6 ]
Briken, Volker [7 ,8 ]
Moody, D. Branch [1 ]
机构
[1] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA
[2] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA
[3] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm Med, Boston, MA 02115 USA
[4] Boston Univ, Sch Med, Boston, MA 02118 USA
[5] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Immunol & AIDS, Boston, MA 02115 USA
[6] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA
[7] Univ Maryland, Maryland Pathogen Res Inst, College Pk, MD 20742 USA
[8] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA
基金
美国国家卫生研究院;
关键词
T-CELL RECOGNITION; MHC CLASS-II; DIFFERENT INTRACELLULAR COMPARTMENTS; MYCOBACTERIUM-TUBERCULOSIS; LIPID ANTIGENS; CRYSTAL-STRUCTURE; CATHEPSIN-S; GLYCOLIPID ANTIGENS; CYSTEINE PROTEASES; VIRAL INFECTIVITY;
D O I
10.1084/jem.20082480
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1409 / 1422
页数:14
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