Chemical biology of antigen presentation by MHC molecules

Curr Opin Immunol. 2014 Feb;26:21-31. doi: 10.1016/j.coi.2013.10.005. Epub 2013 Nov 14.


MHC class I and MHC class II molecules present peptides to the immune system to drive proper T cell responses. Pharmacological modulation of T-cell responses can offer treatment options for a range of immune-related diseases. Pharmacological downregulation of MHC molecules may find application in treatment of auto-immunity and transplantation rejection while pharmacological activation of antigen presentation would support immune responses to infection and cancer. Since the cell biology of MHC class I and MHC class II antigen presentation is understood in great detail, many potential targets for manipulation have been defined over the years. Here, we discuss how antigen presentation by MHC molecules can be modulated by pharmacological agents and how chemistry can further support the study of antigen presentation in general. The chemical biology of antigen presentation by MHC molecules shows surprising options for immune modulation and the development of future therapies.

Publication types

  • Review

MeSH terms

  • Antigen Presentation / immunology*
  • Drug Design
  • Endoplasmic Reticulum / chemistry
  • Endoplasmic Reticulum / enzymology
  • Endoplasmic Reticulum / immunology
  • Histocompatibility Antigens Class I / chemistry*
  • Histocompatibility Antigens Class I / metabolism*
  • Histocompatibility Antigens Class II / chemistry*
  • Histocompatibility Antigens Class II / metabolism*
  • Host-Pathogen Interactions
  • Humans
  • Peptide Fragments / biosynthesis
  • Proteasome Endopeptidase Complex / chemistry
  • Proteasome Endopeptidase Complex / metabolism
  • Proteasome Endopeptidase Complex / physiology
  • Protein Binding / immunology
  • Substrate Specificity / immunology
  • Vaccines, Subunit / chemical synthesis
  • Vaccines, Subunit / metabolism


  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Peptide Fragments
  • Vaccines, Subunit
  • Proteasome Endopeptidase Complex