Origin and Processing of MHC Class II Ligands

Colin Watts, Bénédicte Manoury

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)


Unlike class I MHC, which, as described elsewhere in this encyclopedia, assembles with peptide in the ER, class II MHC engages peptides in endosomes and lysosomes and therefore provides a read out of proteins that enter that pathway whether they be from endocytosed pathogens and/or their products or self-proteins that have gained access to the pathway. Class II MHC molecules only operate effectively when two dedicated chaperones are coexpressed. First, newly translated and ER-translocated class II MHC alpha and beta chains assemble with a type II membrane protein called invariant chain (Ii), invariant because it does not show the polymorphism characteristic of MHC proteins themselves. Ii acts as both a guardian of the peptide-binding site during the early stages of class II MHC biosynthesis and as a targeting subunit, which ensures delivery of class II to the endo-lysosome system. Here, the Ii is removed by a combination of proteolysis and the action of a second key chaperone DM which as outlined below catalyzes replacement of the residual Ii peptide (CLIP) with an antigenic or self-peptide. Peptides generated in lysosomes by different sets of proteases are loaded on class II MHC molecules and travel to the cell surface where they have an extended lifetime except in immature DC (see below). Class II MHC-associated peptides have no formal constraint on their length (unlike those on class I MHC-associated peptide, normally 8-10 residues) because the binding groove is open-ended.

Original languageEnglish
Title of host publicationEncyclopedia of Immunobiology
EditorsMichael J.H. Ratcliffe
PublisherElsevier Inc.
Number of pages6
ISBN (Print)9780080921525
Publication statusPublished - 2016


  • AEP
  • Antigen presentation
  • Antigen processing
  • Cathepsins
  • Dendritic cells
  • DM
  • DO
  • GILT
  • Ii
  • Lysosomes
  • Major histocompatibility complex
  • MHC II
  • NADPH oxidase
  • TFEB
  • Ubiquitination

ASJC Scopus subject areas

  • General Medicine


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