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Purification of the Membrane Compartment for Endoplasmic Reticulum-associated Degradation of Exogenous Antigens in Cross-presentation
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Rapid intracellular pathway gives rise to cell surface expression of the MHC class II-associated invariant chain

N Koch1, G Moldenhauer, W J Hofmann

  • 1Institute of Immunology and Genetics, German Cancer Research Center, Heidelberg.

Journal of Immunology (Baltimore, Md. : 1950)
|October 15, 1991
PubMed

Insights

Invariant chain (Ii) is expressed on the surface of B lymphocytes and lymphoma cells. This surface invariant chain (sIi) remains associated with class II molecules, challenging previous models of their separation.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Previous studies indicated that class II molecules and invariant chain (Ii) follow a delayed endocytic pathway.
  • Invariant chain (Ii) was thought to be degraded in post-Golgi compartments, with only class II molecules reaching the cell surface.

Purpose of the Study:

  • To investigate the surface expression of invariant chain (Ii) on human B lymphocytes and lymphoma cells.
  • To examine the association of invariant chain (Ii) with class II molecules on the cell surface.
  • To understand the intracellular transport and regulation of surface invariant chain (sIi).

Main Methods:

  • Utilized a monoclonal antibody (mAb) against the extracytoplasmic domain of human Ii.
  • Employed electron microscopy and cytofluorometry to detect surface Ii.
  • Investigated the effects of brefeldin A and chloroquine on Ii transport and surface expression.

Main Results:

  • Demonstrated surface expression of invariant chain (Ii) on lymphoma cells and human B lymphocytes.
  • Brefeldin A treatment rapidly depleted cell surface Ii, which was quickly reconstituted upon drug removal.
  • Chloroquine inhibited brefeldin A-induced depletion, suggesting a role in preventing Ii internalization.
  • Immunochemical studies revealed that a proportion of Ii and class II polypeptides remain associated on the cell surface.

Conclusions:

  • Invariant chain (Ii) is expressed on the surface of B lymphocytes and lymphoma cells.
  • Surface Ii (sIi) is not proteolytically digested en route to the cell surface.
  • A fraction of invariant chain (Ii) and class II molecules remain associated on the cell surface, suggesting a potential co-transport or co-localization mechanism.

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