Nature Immunology
3, 435 - 442 (2002)
Published online: 8 April 2002; | doi:10.1038/ni780
Lipid length controls antigen entry into endosomal and nonendosomal pathways for CD1b presentationD. Branch Moody1, Volker Briken2, Tan-Yun Cheng1, Carme Roura-Mir1, Mark R. Guy3, David H. Geho4, Mark L. Tykocinski5, Gurdyal S. Besra3
& Steven A. Porcelli21
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Smith Building Room 514, 1 Jimmy Fund Way, Boston, MA 02115, USA. 2
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Room 416 Forchheimer Building, 1300 Morris Park Avenue, Bronx, NY 10461, USA. 3
Department of Microbiology and Immunology, The Medical School, University of Newcastle Upon Tyne, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK. 4
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. 5
Department of Pathology, University of Pennsylvania, 6 Gates Pavillion, 3400 Spruce Street, Philadelphia, PA 19104, USA.
Correspondence should be addressed to D. Branch Moody bmoody@rics.bwh.harvard.eduCD1 proteins present various glycolipid antigens to T cells, but the cellular mechanisms that control which particular glycolipids generate T cell responses are not understood. We show here that T cell recognition of glucose monomycolate antigens with long (C80) alkyl chains involves the delivery of CD1b proteins and antigens to late endosomes in a process that takes several hours. In contrast, analogs of the same antigen with shorter (C32) alkyl chains are rapidly, but inefficiently, presented by cell surface CD1b proteins. Dendritic cells (DCs) preferentially present long-chain glycolipids, which results, in part, from their rapid internalization and selective delivery of antigens to endosomal compartments. Nonprofessional antigen-presenting cells, however, preferentially present short-chain glycolipids because of their lack of prominent endosomal presentation pathways. Because long alkyl chain length distinguishes certain microbial glycolipids from common mammalian glycolipids, these findings suggest that DCs use a specialized endosomal-loading pathway to promote preferential recognition of glycolipids with a more intrinsically foreign structure.
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