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Recycling CD1d1 molecules present endogenous antigens processed in an endocytic compartment to NKT cells

Tonya J Roberts1, Venkataraman Sriram, Philip M Spence

  • 1Department of Microbiology and Immunology, Indiana University School of Medicine and Walther Oncology Center, Indianapolis, IN 46202, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|May 23, 2002
PubMed

Insights

Mouse CD1d1 molecules require an acidic endocytic pathway for presenting glycolipid antigens to NKT cells. This process involves cell surface CD1d1 delivery and an acidic environment for proper antigen loading.

Area of Science:

  • Immunology
  • Cell Biology
  • Glycolipid Antigen Presentation

Background:

  • Mouse CD1d1 molecules present endogenous glycolipids to NKT cells.
  • Glycolipid presentation by CD1d1 involves transport through the endocytic pathway.
  • Processing requirements for endogenous antigen presentation by CD1d1 are not fully understood.

Purpose of the Study:

  • To investigate the endocytic processing requirements for CD1d1-mediated glycolipid antigen presentation to NKT cells.

Main Methods:

  • Utilized recombinant vaccinia viruses to express normal and mutated mouse CD1d1.
  • Disrupted endocytic trafficking and function using chemical inhibitors (chloroquine, bafilomycin A1, primaquine).
  • Assessed NKT cell recognition of CD1d1-presented antigens.

Main Results:

  • Preventing CD1d1 endosomal localization abrogated Valpha14Jalpha281(+) NKT cell recognition.
  • Inhibiting acidic compartments (increasing pH) blocked Valpha14(+) NKT cell recognition without reducing cell surface CD1d1.
  • Primaquine treatment also interfered with CD1d1 recognition, suggesting a role for recycling.

Conclusions:

  • CD1d1 antigen loading requires an acidic endocytic environment.
  • Cell surface CD1d1 delivery to endosomes is crucial for presenting a subset of glycolipid ligands to NKT cells.

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