Glycosyl-phosphatidylinositol reanchoring unmasks distinct antigen- presenting pathways for CD1b and CD1c

David H. Geho, John D. Fayen, Robin M. Jackman, D. Branch Moody, Steven A. Porcelli, Mark L. Tykocinski

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Human CD1 proteins present lipid and glycolipid Ags to T cells. Cellular trafficking patterns of CD1 proteins may determine the ability of differing isoforms of CD1 to acquire, bind, and present these Ags to T cells. To test this hypothesis, glycosyl-phosphatidylinositol (GPI)-modified variants of CD1b and CD1c were engineered by chimerization with a GPI modification signal sequence derived from decay-accelerating factor (DAF). GPI reanchoring was confirmed by demonstrating the phosphatidylinositol-specific phospholipase C sensitivity of the CD1b · DAF and CD1c · DAF fusion proteins expressed on transfectant cell surfaces. Using cytotoxicity and cytokine release assays as functional readouts, we demonstrated that CD1c · DAF is as efficient as native CD1c in presenting mycobacterial Ags to the human CD1c-restricted T cell line CD8-1. In contrast, CD1b · DAF, although also capable of presenting Ag (in this case to the CD1b-restricted T cell line LDN5), was less efficient than its native CD1b counterpart. The data support the idea that CD1c · DAF maintains the capacity to access CD1c Ag-loading compartment(s), whereas CD1b · DAF is diverted by its GPI anchor away from the optimal CD1b Ag-loading compartment(s). This constitutes the first GPI reanchoring of CD1 proteins and provides evidence that CD1b and CD1c have nonoverlapping Ag-presenting pathways, suggesting that these two Ag- presenting molecules may have distinct roles in lipid Ag presentation.

Original languageEnglish (US)
Pages (from-to)1272-1277
Number of pages6
JournalJournal of Immunology
Volume165
Issue number3
DOIs
StatePublished - Aug 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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