Class I MHC molecules: assembly and antigen presentation

Immunol Rev. 1999 Dec;172:11-9. doi: 10.1111/j.1600-065x.1999.tb01352.x.


Several years ago, the only factor known to be necessary for the assembly and surface expression of class I MHC was beta 2m; even for beta 2m, it was unclear at what point in class I maturation its role was played. Recent experiments that employed attachment of an endoplasmic reticulum (ER) retention signal to beta 2m have shown that the point of time at which beta 2m is required is while the class I heavy chain is in the ER. Later association between beta 2m and class I is not vital in order for properly folded class I to be expressed at the cell surface. After crystallization of the first class I MHC molecule, it was realized that not only is antigen presented by class I, but that antigen is presented in the form of a peptide that stabilizes the class I structure and allows its transit to the cell surface. Class I allelic differences influence interactions with both peptide and beta 2m, with likely consequences for the ability of the class I heavy chains to present antigen through alternative pathways. Furthermore, it is now also clear that formation of appropriate disulfide bonds in the class I heavy chain is needed before class I can bind peptide antigen securely, a process that may be assisted by an ER chaperone. Many different proteins that are resident in the ER, such as calnexin, transporter associated with antigen processing (TAP), calreticulin, and tapasin, have been found to be integral to class I assembly. TAP, tapasin, and calreticulin bind preferentially to the open form of class I, which can be distinguished with the use of a monoclonal antibody specific for this form. Calreticulin and calnexin contrast in their interactions with class I, despite other similarities between these two chaperones. Overall, class I MHC assembly is now understood to involve the interplay of multiple intra- and intermolecular events in a defined chronological order which ensure continual reporting of cellular contents to cytotoxic T lymphocytes.

Publication types

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

MeSH terms

  • Alleles
  • Animals
  • Antigen Presentation*
  • Antiporters / metabolism
  • Calcium-Binding Proteins / metabolism
  • Calnexin
  • Calreticulin
  • Endoplasmic Reticulum / immunology
  • Endoplasmic Reticulum / metabolism
  • Histocompatibility Antigens Class I / chemistry*
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Immunoglobulins / metabolism
  • Macromolecular Substances
  • Membrane Transport Proteins
  • Models, Molecular
  • Protein Conformation
  • Ribonucleoproteins / metabolism
  • beta 2-Microglobulin / metabolism


  • Antiporters
  • Calcium-Binding Proteins
  • Calreticulin
  • Histocompatibility Antigens Class I
  • Immunoglobulins
  • Macromolecular Substances
  • Membrane Transport Proteins
  • Ribonucleoproteins
  • beta 2-Microglobulin
  • tapasin
  • Calnexin