Role of lipid trimming and CD1 groove size in cellular antigen presentation

Tan Yun Cheng, Miguel Relloso, Ildiko Van Rhijn, David C. Young, Gurdyal S. Besra, Volker Briken, Dirk M. Zajonc, Ian A. Wilson, Steven Porcelli, D. Branch Moody

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Cellular CD1 proteins bind lipids that differ in length (C 12-80), 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.

Original languageEnglish (US)
Pages (from-to)2989-2999
Number of pages11
JournalEMBO Journal
Volume25
Issue number13
DOIs
StatePublished - Jul 12 2006

Keywords

  • Antigen processing
  • CD1
  • T cells
  • Tuberculosis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Cheng, T. Y., Relloso, M., Van Rhijn, I., Young, D. C., Besra, G. S., Briken, V., Zajonc, D. M., Wilson, I. A., Porcelli, S., & Moody, D. B. (2006). Role of lipid trimming and CD1 groove size in cellular antigen presentation. EMBO Journal, 25(13), 2989-2999. https://doi.org/10.1038/sj.emboj.7601185