The MHC I loading complex: a multitasking machinery in adaptive immunity

Trends Biochem Sci. 2013 Aug;38(8):412-20. doi: 10.1016/j.tibs.2013.06.003. Epub 2013 Jul 10.

Abstract

Recognition and elimination of virally or malignantly transformed cells are pivotal tasks of the adaptive immune system. For efficient immune detection, snapshots of the cellular proteome are presented as epitopes on major histocompatibility complex class I (MHC I) molecules for recognition by cytotoxic T cells. Knowledge about the track from the equivocal protein to the presentation of antigenic peptides has greatly expanded, leading to an astonishingly elaborate understanding of the MHC I peptide loading pathway. Here, we summarize the current view on this complex process, which involves ABC transporters, proteases, chaperones, and endoplasmic reticulum (ER) quality control. The contribution of individual proteins and subcomplexes is discussed, with a focus on the architecture and dynamics of the key player in the pathway, the peptide-loading complex (PLC).

Keywords: ABC transporters; ER quality control; MHC class I molecules; chaperones; macromolecular complexes; proteasome; tapasin; transporter associated with antigen processing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptive Immunity*
  • Animals
  • Antigen Presentation
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism*
  • Endoplasmic Reticulum / metabolism
  • Genes, MHC Class I*
  • Humans
  • Models, Biological*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism