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MHC molecules are key players in the immune response, enabling T cells to recognize and respond to specific antigens. They are present on the surface of all nucleated cells in the body and are instrumental in presenting antigens to T cells and activating them. T cells recognize the MHC-antigen complex and initiate an immune response. MHC class I and MHC class II are two main types of MHC molecules, each associated with a distinct antigen processing pathway.
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MHC class II antigen presentation by dendritic cells regulated through endosomal sorting.

Toine ten Broeke1, Richard Wubbolts, Willem Stoorvogel

  • 1Utrecht University, Faculty of Veterinary Medicine, Department of Biochemistry and Cell Biology, Yalelaan 2, 3584 CM, Utrecht, The Netherlands.

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Summary

Dendritic cell activation regulates adaptive immunity by controlling major histocompatibility complex class II (MHCII) trafficking. Activated cells prevent MHCII degradation, promoting T cell responses.

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Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Dendritic cells initiate adaptive immunity by presenting antigens via major histocompatibility complex class II (MHCII) to CD4(+) T cells.
  • Regulation of MHCII antigen presentation is crucial for immune response initiation.

Purpose of the Study:

  • To review the intracellular processing and trafficking mechanisms that regulate MHCII presentation by dendritic cells.
  • To highlight the role of ubiquitination and the ESCRT machinery in controlling MHCII surface expression.

Main Methods:

  • Review of existing literature on MHCII processing, trafficking, and ubiquitination in dendritic cells.
  • Focus on the ESCRT machinery's role in sorting MHCII within multivesicular bodies.

Main Results:

  • Newly synthesized MHCII is chaperoned by the invariant chain to endosomes for peptide loading.
  • In nonactivated dendritic cells, ubiquitination targets peptide-loaded MHCII for degradation via the ESCRT pathway.
  • Upon dendritic cell activation, MHCII ubiquitination is blocked, enabling surface presentation.

Conclusions:

  • Dendritic cell activation status dictates MHCII fate through regulated ubiquitination and sorting.
  • Multivesicular body sorting is a key regulatory point controlling cell surface receptor expression, exemplified by MHCII.