Article
- The EMBO Journal (2006) 25, 2989 - 2999
- doi:10.1038/sj.emboj.7601185
Published online: 22 June 2006
Subject Categories:
Role of lipid trimming and CD1 groove size in cellular antigen presentation
Tan-Yun Cheng1, Miguel Relloso1, Ildiko Van Rhijn2, David C Young1, Gurdyal S Besra3, Volker Briken4, Dirk M Zajonc5, Ian A Wilson6,7, Steven Porcelli4 and D Branch Moody1
- Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Department of Infection and Immunity, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
- School of Biosciences, The University of Birmingham, Edgbaston, Birmingham, UK
- Department of Immunology and Microbiology, Albert Einstein College of Medicine, Bronx, NY, USA
- Division of Cellular Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA
- Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA, USA
- Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA
Correspondence to:
D Branch Moody, Division of Rheumatology Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Smith Building 514, 1 Jimmy Fund Way, Boston, MA 2115, USA. Tel.: +1 617 525 1037; Fax: +1 617 525 1010; E-mail: bmoody@rics.bwh.harvard.edu
Received 5 January 2006; Accepted 16 May 2006
Abstract
Cellular CD1 proteins bind lipids that differ in length (C12-80), including antigens that exceed the capacity of the CD1 groove. This could be accomplished by trimming lipids to a uniform length before loading or by inserting each lipid so that it penetrates the groove to a varying extent. New assays to detect antigen fragments generated within human dendritic cells showed that bacterial antigens remained intact, even after delivery to lysosomes, where control lipids were cleaved. Further, recombinant CD1b proteins could bind and present C80 lipid antigens using a mechanism that did not involve cellular enzymes or lipid cleavage, but was regulated by pH in the physiologic range. We conclude that endosomal acidification acts directly, rather than through enzymatic trimming, to insert lipids into CD1b. Lipids are loaded in an intact form, so that they likely protrude through a portal near the bottom of the groove, which represents an escape hatch for long lipids from mycobacterial pathogens.
Keywords:
- antigen processing,
- CD1,
- T cells,
- tuberculosis
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